Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Herbal and Botanical

Cola

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)

Extra-luminal (serosa) and Endo-luminal (mucosal) evaluation of the proximal colon and distal rectal stump perfusion based on a semi-quantitative NIR-ICG-induced FA. This will be conducted administering IV a bolus of 3.75 to 7.5 mg of ICG and evaluated using a Fluorescence Imaging System; following after completion of the anastomosis a second bolos of 3.75 to 7.5 mg of ICG will be administered IV and the anastomosis will be visualized by insertion of the system trans-anally. Colon and rectal segments and quadrants will be scored for any defect of perfusion.

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

This will be conducted insufflaying air in the anastomosis through a proctoscope, tube or a flexible endoscope, after filling of the pelvis with saline solution and luminal occlusion of the intestine proximal to the anastomosis. Also, the anastomosis will be checked transanally for the presence of air leak.

Air Leak test

The assessment of the anastomotic rings following mechanical anastomosis will be recorded as complete/incomplete

Evaluation of the anastomotic rings

Roberto Persiani, MD

Laura Lorenzon, MD PhD

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.

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

Rectal Cancer Anastomosis 4 Check Study

Rectal Cancer 4 Check Study

defined as additional suturing or re-do anastomosis

defined as anastomotic-related morbidity, including anastomotic leakage, pelvic abscess, anastomotic-related fistula, sinus, and anastomotic stricture

Costs resource utilization for the procedure

measurement conducted in postoperative days 1, 3 \& 5 (optional) using mg/L

measurement conducted in postoperative days 1, 3 \& 5 (optional) using mg/L ng/mL

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rare Diseases

Esophageal Neoplasms

Esophageal Cancer

Q-ICG: quantitative perfusion assessment with FA White light perfusion assessment FA: fluorescence angiography without quantification

Quantitative perfusion assessment with indocyanine green on a touch screen tablet

Q-ICG

Traditional visual perfusion assessment in white light

White light perfusion assessment

Perfusion assessment with fluorescence angiography - without quantification

Fluorescence angiography

Michael P Achiam, MD,PhD,DMSci

This study will investigate a new method to assess tissue perfusion during surgery for esophageal cancer.

When a tumor in the distal esophagus is removed, the ends of the esophagus and the stomach must be reconnected by an anastomosis. An optimal perfusion is essential to ensure a good healing of the anastomosis. If anastomotic leakage occurs, it may prolong hospital stay, increase the risk of serious complications and death, delay start-up of chemotherapy and worsen the long-term survival prognosis.

During the operation the blood supply to the ends of the esophagus and stomach will be assessed in different ways; The traditional where the surgeon looks and feels on the tissue, and newer methods with an indocyanine green and cameras that illuminate the tissue with near-infrared light. The surgeon will assess whether these methods change the decision on where the ends should be sewn together.

Introduction:

An optimal perfusion is essential in gastrointestinal surgery when resection of a cancerous tissue requires an anastomosis, since impaired perfusion seems to be associated with increased risk of anastomotic leakage (AL). AL is a severe complication with the risk of; prolonged hospital stay, cancer recurrence, permanent stoma in colorectal surgery, and increased short and long-term mortality. To avoid poor perfusion of an anastomosis, perfusion assessment is necessary during the operative procedure. Traditionally, perfusion is assessed visually and manually by the surgeon by judging the; color of the tissue, bleeding from the resection line, and the arterial supply pulse by palpation. These methods have earlier been shown to be unreliable and prone to observer bias. Furthermore, palpation of arterial supply is not possible in laparoscopic or robot-assisted surgery, and the increased use of staplers to divide the bowel leaves no bleeding resection lines. Therefore newer methods for perfusion assessment have been investigated, and fluorescence angiography (FA) and laser speckle contrast imaging (LSCI) has shown very promising results. In a systematic review of nonrandomized studies, the leakage rate in 916 colorectal resections was significantly lower when using FA compared to controls (3.3%, \[95% CI: 1.97-4.63%\] vs 8.5%, \[95% CI: 4.8-12.2%\], p=0.0055).

In FA, the tissue of interest is exposed to near-infrared (NIR) light simultaneously with intravenous injection of a fluorescent dye. When the dye reaches the illuminated area, it fluoresces, and a camera with a special filter can visualize the microcirculation of the tissue on a monitor. Many NIR-camera systems are on the market, combining the technique with conventional laparoscopic or robotic equipment, and several non-randomized studies have indicated that FA may reduce the anastomotic leakage rate in gastrointestinal surgery. Most surgeons are using only a visual subjective assessment of the FA, which may be prone to observer bias. Moreover, if the camera is not held at a standard distance from the tissue, or a different concentration of dye is used, a false negative or positive assessment of the perfusion may be made. Therefore, it has been argued that there is a need for an objective unbiased quantitative assessment tool in FA.

A quantification algorithm that provides a fluorescence-time curve and a quantitative parameter of perfusion, the normalized slope has previously been published, where a nearly linear correlation to regional flow was found. Until now measurements has been performed as analyses of video-recordings after the procedure.

In order to use the method in a clinical setting, development and testing of a tool that may be operated by the surgeon during the procedure to perform perioperative measurements is of high importance. A touchscreen tablet has been developed, in order to perform live perioperative quantitative perfusion assessment using FA. The tool may be used with several systems including Karl Storz fluorescence laparoscopic equipment and the daVinci SI or XI from Intuitive. This tool is essential in order to implement the technology into daily practice, as it allows the surgeon to get an immediate quantitative parameter of perfusion (normalized slope) at desired regions of interest. The interface of the tool should be easy to use and provide fluorescence-time curves to control the automated calculation of the normalized slope. In addition, a color-coded map of perfusion intensity should be provided as an overlay on the white light picture of the bowel investigated.

Aim:

The touchscreen tablet has currently only been tested in animal surgery. The aim of the present study is to investigate if the use of a perioperative quantitative perfusion assessment tool may improve the perfusion assessment during surgery in humans.

Hypotheses:

* Perioperative perfusion assessment with FA will change the point of resection determined by conventional visual perfusion assessment in GI junctional procedures.
* Quantitative perfusion assessment with FA (Q-ICG) will further change the point of resection determined by visual assessment of the FA and conventional visual assessment of perfusion in GI junctional procedures.

Primary endpoints:

* Feasibility of perfusion assessment with traditional visual, visual FA, and Q-ICG - complied by completion rates.
* The feasibility and usability of the tool, the surgeons' experiences with the Q-ICG-tablet interface - rated on a validated questionnaire, the System Usability Scale.

Secondary endpoints:

• Differences in the distance from the determined resection points using traditional assessment, FA, and Q-ICG.

Methods

Study Design:

The study will be conducted as an observational feasibility and usability trial in patients undergoing open or robot-assisted resection of the gastroesophageal junction (GI junction) in a single university hospital center (Rigshospitalet, Department of Surgical Gastroenterology). Patients will serve as their own control. Demographic information (tumor-staging, gender, age, BMI, neoadjuvant treatment, ASA-classification, smoking, alcohol, medication etc.) will be collected from the electronic patient records. In addition, postoperative events, especially the presence of an anastomotic leakage, will be noted 30 days postoperatively. No formal sample size calculation has been performed as the study is a feasibility study. 20 patients will be included. Participating patients will receive the same standard post- and peri-operative care and follow-up as patients not included in the study.

Indocyanine green Indocyanine green (ICG) is a well-described nontoxic tricarbocyanine dye used for decades in ophthalmology, cardiology, and hepatology. Very few mild adverse reactions have been reported, but caution in patients with thyrotoxicosis, allergy towards iodine or indocyanine green should be made. When injected intravenously it binds to blood lipoproteins and is solely metabolized by the liver and excreted in the bile, with a short half-life of approximately 4-5 minutes.

Surgical procedure and perfusion assessment When the dissection and division of the feeding blood vessels are complete and the gastric conduit established and drawn to the thorax, the gastrointestinal surgeon will choose the most proximal point possible on the conduit for the anastomosis (Anastomotic point surgeon, APS) by pointing while a picture is captured, blinded for the thoracic surgeon. A sterile paper ruler will be introduced to the thorax, in order to measure the distance between the chosen resection points. Then, LSCI measurement of the conduit is performed, and finally, a bolus of ICG (0.25 mg/kg body weight) will be injected intravenously and flushed with 5 mL of saline, and the tissue of interest exposed to NIR-light (excitation wavelength 750-800 nm) and emission observed at 800 nm (FA). During the video-captures of LSCI and ICG-FA, the respiration will be paused for a maximum of 20 seconds initiated at the moment of saline injection. After the FA the thoracic surgeon will by visual assessment determine and mark a new anastomotic point by pointing at the most proximal point possible on the conduit for the anastomosis, while a picture is taken (anastomotic point fluorescence angiography, APFA). After the quantitative FA the surgeon will again mark an anastomotic point (APQFA). The final anastomotic point will be chosen by the primary gastrointestinal and the thoracic surgeon, and if the assessment of FA or quantitative FA will influence this decision is solely up to the surgeon. The same points will be marked on the LSCI picture but not revealed to the surgeon since the quantitative assessment of the LSCI demands on post hoc data-analysis.

When the surgeon decides how much tissue to resect to ensure an optimal anastomotic perfusion, care must be taken not to cause tension to the anastomosis by resecting too much of the gastric conduit or the esophagus, as tension is a known risk factor of anastomotic leakage. Again, the level of resection is solely decided by the surgeon and this decision should, as always, be made by balancing factors of tension, perfusion, and excessive tissue loss - all combined to ensure an optimal anastomotic healing.

Laparoscopic fluorescence angiography A laparoscope (ICG-Hopkins telescope 30°, 10 mm, Karl Storz Gmbh and Co. KG, Tüttlingen, Germany) will be connected to a camera system (IMAGE1, Karl Storz Gmbh and Co. KG, Tüttlingen, Germany) and a light-source (D-light P, Karl Storz Gmbh and Co. KG, Tüttlingen, Germany) will supply the excitatory light and record the FA. The laparoscope will be fixed in a mechanical holding arm 10 cm from the tissue of interest, ensuring a stable position throughout the experiment.

Robot-assisted fluorescence angiography A surgical robot DaVinci SI (Intuitive Surgical Inc., Sunnyvale, CA, USA) and the Firefly Fluorescence Imaging system will be used. The camera will be fixed 10 cm from the tissue of interest, ensuring a stable position throughout the experiment.

Quantitative fluorescence angiography (Q-ICG) A video capture device (Av.io HD™, Epiphan video, California, USA) will be connected to the surgical robot or the laparoscopic camera system and transfer the video capture to a tablet (Microsoft Surface Pro4 I5, Microsoft, Redmond, WA, USA). A program developed to quantify the FA will be installed. Here the operator can choose regions of interest to quantify from the captured video sequence. A color grading of perfusion will be provided as well as quantitative values from specific points. From this assessment, the surgeon will again determine a new resection point (APQFA).

Comparison of resection points The distance from the tumor to the RPS will be measured before the FA using the paper ruler. In addition, the distance from the APS to APFA and APQFA will be measured using the ruler, either during the procedure or post hoc using the video-capture. The comparison of the distance will be made on the distance of each point from the tumor.

Feasibility The feasibility will be investigated by comparison of completion rates of the different perfusion assessment methods; traditional, FA, Q-ICG.

Usability The usability of the quantitative perfusion assessment tool will be investigated with a validated questionnaire, the System Usability Scale, answered by the surgeon immediately after the procedure.

Statistics Comparison of data will be performed using Mann Whitney U test or a paired sample t-test depending on distribution normality. P-values \< 0.05 is considered significant. No formal sample size calculation has been made, as the study is considered a feasibility trial. 20 patients will be recruited. Statistic evaluation was performed using IBM SPSS Statistics © (v 22.0 SPSS Inc. Chicago, IL, USA).

Adverse events, risks, and disadvantages Adverse events associated with the use of ICG are extremely rare and severe anaphylactic reactions are almost never occurring. However, safety precautions have been made by excluding patients with allergy to iodine, ICG or shellfish. In addition, no patients with liver insufficiency, thyrotoxicosis, ongoing pregnancy, or lactating women will be included.

Perioperative Perfusion Measurement - a Feasibility and Usability Study

Feasibility of perfusion assessment with traditional visual, visual FA, and Q-ICG

Differences in the distance from the determined resection points using traditional assessment, LSCI, FA, and quantitative FA.

The feasibility and usability of the tool, the surgeons' experiences with the Q-ICG tablet interface - rated on a validated questionnaire, the System Usability Scale - https://www.usability.gov/how-to-and-tools/methods/system-usability-scale.html.

Scores ranges from 0-100, where a score of 68 is considered average.

Rigshospitalet, Denmark

PhD-fellow, senior resident

Nervous System Diseases

Neuroma

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Subjects will receive Intravenous ICG to generate a Fluorescence Angiogram of the Neuroma

Intravenous administration of indocyanine green followed by fluorescence angiography imaging of the neuroma

Indocyanine green

Gregory A Dumanian, MD

The purpose of this study is to characterize the perfusion of neuromas using indocyanine green fluorescence angiography

Neuromas represent the frustrated regeneration of injured nerve axons encased in a bulbous scar. Symptomatic neuromas are particularly problematic in patients with amputations. Targeted Muscle Reinnervation is a novel surgical approach to neuroma treatment, resulting in improved residual limb pain in amputees. Nevertheless, a subset of Targeted Muscle Reinnervation patients achieve inadequate relief. Incomplete neuroma excision may be of particular concern in such cases, as failure to completely excise the neuroma risks leaving a scarred proximal nerve stump behind. Despite the critical importance of complete neuroma excision, there is no clear definition of a neuroma's "zone of injury". Indeed, intraoperatively determining where to cut a nerve to ensure accurate and complete excision of a neuroma at the time of reconstruction or repair is an unsolved problem in peripheral nerve surgery. The proposed research aims to characterize the perfusion of neuromas using fluorescence angiography. Specifically, we will test the hypothesis that intravascular indocyanine green (ICG) renders visible the perturbations in nerve perfusion associated with neuromas, and that these altered perfusion patterns correlate with the nerve's "zone of injury" as identified by histopathology. Ultimately, indocyanine green (ICG) fluorescence angiography may facilitate intraoperative decision-making at the time of neuroma excision.

Evaluation of Neuroma Perfusion With Indocyanine Green Fluorescence Angiography

Individual Participant Data that underlie results in a publication

Nerve Tissue Perfusion as visualized by Fluorescence Angiogram

American Society for Surgery of the Hand

Northwestern University

Chief of Plastic surgery in the Department of Surgery

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Carcinoma

Mouth Neoplasms

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Colonic Diseases

Esophageal Diseases

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

Tongue Cancer

Fluorodeoxyglucose F18

Radiopharmaceuticals

18F-fluoromisonidazole

fluorescence angiography

laboratory biomarker analysis

infrared thermography

magnetic resonance imaging

therapeutic conventional surgery

[18F]-ML-10

fludeoxyglucose F 18

rubidium Rb-82

Contact Person

Peter Ell, MD

RATIONALE: Diagnostic procedures, such as positron emission tomography/computed tomography (PET/CT) scanning before surgery, may help measure the extent of disease.

PURPOSE: This clinical trial is studying PET/CT scanning before surgery in patients with non-small cell lung cancer, colorectal cancer, breast cancer, esophageal cancer, or head and neck cancer.

OBJECTIVES:

* To determine the ability of preoperative fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) scanning in assessing tumor angiogenesis in patients with potentially operable non-small cell lung cancer, colorectal cancer, breast cancer, esophageal cancer, or head and neck cancer.
* To determine the ability of preoperative fludeoxyglucose F 18 PET/CT scanning in assessing prognosis by means of measuring angiogenesis in these patients.

OUTLINE: All patients undergo fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) scanning for staging, tumor perfusion measurement/angiogenesis, and glucose metabolism. If staging confirms operable disease, then the patient proceeds to surgery as planned. Resected tumor tissue samples are examined for tumor angiogenesis in the various cancer types.

Some patients undergo a half-dose of rubidium Rb-82 or 18F-fluoromisonidazole or \[18F\]-ML-10 PET scan or fluorescence angiography. Patients with colorectal cancer undergo a CT scan for perfusion of the tumor after the staging PET/CT. Patients with breast cancer undergo infrared thermometry as well as a MRI scan for staging and to predict angiogenesis.

After completion of study therapy, patients are followed up at 1 month and then every 6 months for 5 years.

Positron Emission Tomography/Computed Tomography Scanning Before Surgery in Patients With Non-Small Cell Lung Cancer, Colorectal Cancer, Breast Cancer, Esophageal Cancer, or Head and Neck Cancer

Tumor Angiogenesis in Non-Small Cell Lung (NSCLC), Colorectal, Breast, Esophageal, Head and Neck Cancer: Radiology-Pathology and Prognostic Correlation

University College London (UCL) Cancer Institute

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Colic

Anastomotic Leak

Postoperative Complications

Experimental arm = surgery with IOFA.

In the experimental arm, cancer resection and anastomosis will be performed after assessment of descending colon perfusion using intravenous injection of indocyanine green 0.1ml/kg.

Control arm = Surgery without IOFA.

In the control arm, cancer resection and anastomosis will be performed without intraoperative fluorescence angiography.

In the experimental arm (FLUO+), at least one 0.1mg/kg Infracyanine® bolus will be injected intravenously by the anesthesiologist.

The detection of indocyanine green in the proximal colon segment will be done open or intracorporeally using a dedicated infrared camera.

A surgical film describing the injection technique and fluorescence detection will be presented during the study set-up visits.

An additional injection is allowed at the surgeon's discretion if necessary (change of anastomosis site). The time from injection to indocyanine green detection and any adverse events will be recorded.

FLUO+ : Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG).

Zaher Lakkis, MD, PhD

Jean-Baptiste Pretalli, PhD

Jean-Marc Regimbeau

Olivier OULIE, MD

Zaher Lakkis

Pierre Goubault

Nathan Moreno

David ORRY

Bertrand Trilling

Guillaume Piessen

Benoit Gignoux

Eddy Cotte

Régis Fara

Diane Mege

Cécile De Chaisemartin

Laura Beyer-Berjot

Caroline ROSSI

Frédéric MARCHAL, MD PhD

Leon Maggiori

Jérémie Lefèvre

Mahaut LECONTE

Stéphane BENOIST, MD

Gilles MANCEAU, MD

Nelson Trelles

Cyril Perrenot

Veronique DESFOURNEAUX-DENIS, MD

Jean-Jacques Tuech

Antoine Sina

Benoit Romain

Etienne BUSCAIL, MD

Quentin DENOST, MD PhD

Medhi Ouaissi

Cécilia CERIBELLI, MD

Leonor Benhaim

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world and the third in France. Its incidence is steadily rising in developing nations. Anastomotic leak (AL) is a major problem in colorectal surgery affecting at least 7% of patients operated on for left colonic cancer. It is the most feared complication after colorectal anastomosis, associated with mortality, prolonged hospitalization, impaired health related quality of life (HRQoL) and increased health care costs. Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG) may help preventing AL. Available studies on the effects of IOFA with ICG are heterogeneous and randomized controlled trial are scarce. Our aim is to demonstrate that IOFA with ICG could lead to a reduction of AL rate after left-sided or low anterior resection with anastomosis for CRC.

The FLUOCOL-1 study is the first national, multicenter, single blind, randomized, 2-arm, phase III superiority clinical trial. The primary endpoint is the occurrence of an AL 90 days post-operation. AL is defined as any anastomotic dehiscence with leakage into the pelvic cavity diagnosed upon imaging or at surgical exploration or any isolated pelvic organ-space infection with no evidence of fistula as defined by the International Study Group of Rectal Cancer.

The study population will be made of adult patients with left-sided or high rectal cancer scheduled to undergo elective left colectomy or high rectal resection (by open, laparoscopy or robotic surgery) and with expected stapled or hand-sewn intraperitoneal anastomosis. The exclusion criteria are mainly an emergent surgery; rectal cancer requiring total mesorectal excision and anastomosis expected below the peritoneal reflection; CRC requiring total or subtotal colectomy; CRC requiring transverse colectomy; recurrent CRC and locally advanced colorectal cancer requiring multi-visceral excision.

A total of 1010 patients will be necessary (39 patients in each centre during 36 months). An interim analysis for efficacy and futility is scheduled when half of the participants will have been recruited.

In case of positive results favoring IOFA, this study would define the use of IOFA as a standard of care in colorectal surgery. At the patient level, a significantly lower rate of AL will reduce hospital stay and stoma rate, and will ensure improved postoperative recovery, faster return to normal activity and better long-term oncologic outcomes.

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world and the third in France. Its incidence is steadily rising in developing nations. Anastomotic leak (AL) is a major problem in colorectal surgery affecting at least 7% of patients operated on for left colonic cancer. It is the most feared complication after colorectal anastomosis, associated with mortality, prolonged hospitalization, impaired health related quality of life (HRQoL) and increased health care costs. Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG) may help preventing AL. Available studies on the effects of IOFA with ICG are heterogeneous and randomized controlled trial are scarce. Our aim is to demonstrate that IOFA with ICG could lead to a reduction of AL rate after left-sided or low anterior resection with anastomosis for CRC.

The FLUOCOL-1 study is the first national, multicenter, single blind, randomized, 2-arm, phase III superiority clinical trial. The primary endpoint is the occurrence of an AL 90 days post-operation. AL is defined as any anastomotic dehiscence with leakage into the pelvic cavity diagnosed upon imaging or at surgical exploration or any isolated pelvic organ-space infection with no evidence of fistula as defined by the International Study Group of Rectal Cancer.

The study population will be made of adult patients with left-sided or high rectal cancer scheduled to undergo elective left colectomy or high rectal resection (by open, laparoscopy or robotic surgery) and with expected stapled or handsewn intraperitoneal anastomosis. The exclusion criteria are mainly an emergent surgery; rectal cancer requiring total mesorectal excision and anastomosis expected below the peritoneal reflection; CRC requiring total or subtotal colectomy; CRC requiring transverse colectomy; recurrent CRC and locally advanced colorectal cancer requiring multi-visceral excision.

The 26 participating centres are equipped with a scope with near-infrared (NIR) light source allowing real-time ICG perfusion assessment. The co-investigators are experienced digestive surgeons trained to work with and without IOFA. They have considerable experience in working together on research projects and have a proven track-record of efficacy. Moreover, this study will receive valuable support from the Surgery Research Network (FRENCH) and the Surgical Research on Rectal Cancer Group (GRECCAR), which have proved their ability to recruit patients into various multicentric studies and with which the FLUOCOL-1 project has been discussed.

The duration of participation for each patient is 90 days. The 3 study visits are superimposed to the schedule of standard of care (V1: pre-operation visit of selection and inclusion; Surgery; V2: 30-day post-operation visit and V3: 90-day post-operation visit).

The surgeon will do the 1:1 randomization between V1 and the day before surgery (D-30 to D-1). To reduce the risk of bias, patients will be blinded to the study group and the randomization will be stratified on participating centres, Body Mass Index (BMI), physical status classification score (=ASA score), preoperative treatment and tumor location. Patient will be assigned in the intervention (IOFA) or the control group (no IOFA).

At the exception of the information given on the study to the patient, the gathering of the written consent, the randomization and the HRQoL questionnaires, the patient will be treated following standard of care. Study data are the data systematically collected in the patient medical file except for the HRQoL questionnaires that will be collected under the supervision of a research technician financed by the study. The technician will capture the study data and the de-identified pdf version of the medical reports (consultations and hospitalizations) in the electronic Case Report Form (eCRF) after every visit.

A total of 1010 patients will be necessary (39 patients in each centre during 36 months). An interim analysis for efficacy and futility is scheduled when half of the participants will have been recruited.

The ICG will be graciously provided by the manufacturer (SERB). An investigator meeting will be organized twice a year during the annual GRECCAR and FRENCH meetings. Newsletters will be sent every 3 months.

In case of positive results favoring IOFA, this study would define the use of IOFA as a standard of care in colorectal surgery. At the patient level, a significantly lower rate of AL will reduce hospital stay and stoma rate, and will ensure improved postoperative recovery, faster return to normal activity and better long-term oncologic outcomes.

Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage

Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage: a Single-blind Phase III Multicenter Randomized Controlled Trial (Intergroup FRENCH-GRECCAR Trial)

The primary outcome is the occurence of an anastomotic leakage during the 90 days following surgery.

Anastomotic leakage is defined as any clinical signs of leakage diagnosed by radiological examination or surgical exploration, or as any isolated pelvic organ infection without leakage evidence, as defined by the International Rectal Cancer Study Group.

Change in planned anastomosis during surgery is defined as any decision change on perfusion assessment such as modifying the initially planned transection level of the descending colon or refashioning anastomosis including the decision to undertake a permanent stoma rather than an anastomosis.

The rate of defunctioning stoma created in the initial surgery as a temporary diverting pathway will be calculated.

Overall 30-day postoperative morbidity is defined and classified according to the Clavien-Dindo classification.

Overall 90-day postoperative morbidity is defined and classified according to the Clavien-Dindo classification.

Postoperative reintervention number and type within 90 days.

Health related quality of life is assessed using the quality of life questionnaires : QLQ-C30 and QLQ-CR29 at baseline and 90 days post-operation.

The QLQ-C30 is a patient self-rating questionnaire (30 questions) that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. Scores can be linearly transformed to provide a score from 0 to 100 REF. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.

The QLQ-CR29 (Quality of life of rectal cancer patients with 29 questions) has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items. The score can range from 0 to 100.

Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.

The medico-economic analysis takes into consideration health care costs up until 90 days post-operation.

Centre Hospitalier Universitaire de Besancon

Sigmoid Neoplasms

Colonic Neoplasms

Sigmoid Diseases

A sigmoid and rectum resection with colorectal anastomosis will be performed according to the surgeons standard practice with the addition of intraoperative imaging using fluorescence angiography with indocianyne green to assess colon and rectal tissue perfusion.

A sigmoid and rectum resection with colorectal anastomosis will be performed according to the surgeons standard practice.

The fluorescence angiography was performed after mobilization of the bowel, transection of the rectum, division of the rectal and colon mesentery and central vessels, before specimen extraction or resection and creation of the anastomosis. This site was selected by the surgeon using his or her best judgment and typical standard of care assessment. After this selection, the anesthesiologist administered a bolus of 1 to 2 ml indocianyne green intravenously. Perfusion of the colon was visualized and assessed via fluorescence angiography and the line of demarcation between perfused and nonperfused tissue was noted and compared with the initial planned transection point.

Fluorescence angiography with indocianyne green

This is a randomized, controlled, parallel study to determine the difference in post-operative anastomotic leak rate of colorectal anastomosis where colon and rectal tissue perfusion is evaluated using fluorescence angiography with indocyanine green and without this method.

The design involves random allocation of eligible patients to operation with colorectal anastomosis and intraoperative fluorescence angiography with indocyanine green and operation alone. After surgery on 7-8 POD patients are examined to two sides X-Ray proctography performed by introducing 100 ml of water-soluble liquid contrast material through the anus over the anastomotic line by a Foley catheter for diagnosis of anastomotic leakage.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rectal Cancer Anastomosis 4 Check Study	NCT04637061	Rectal Cancer	intraoperative ... Air Leak test Evaluation of t...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Perioperative Perfusion Measurement - a Feasibility and Usability Study	NCT03671642	Esophageal Canc...	Q-ICG White light per... Fluorescence an...	18 Years -	Rigshospitalet, Denmark
Perioperative Perfusion Measurement - a Feasibility and Usability Study	NCT03671642	Esophageal Canc...	Q-ICG White light per... Fluorescence an...	18 Years -	Rigshospitalet, Denmark
Evaluation of Neuroma Perfusion With Indocyanine Green Fluorescence Angiography	NCT06164392	Neuroma Neuroma Amputat... Neuroma of Uppe... Neuroma of Lowe...	Indocyanine gre...	18 Years -	Northwestern University
Rectal Cancer Anastomosis 4 Check Study	NCT04637061	Rectal Cancer	intraoperative ... Air Leak test Evaluation of t...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Positron Emission Tomography/Computed Tomography Scanning Before Surgery in Patients With Non-Small Cell Lung Cancer, Colorectal Cancer, Breast Cancer, Esophageal Cancer, or Head and Neck Cancer	NCT01254591	Breast Cancer Colorectal Canc... Esophageal Canc... Head and Neck C... Lung Cancer	18F-fluoromison... fluorescence an... laboratory biom... infrared thermo... magnetic resona... therapeutic con... [18F]-ML-10 fludeoxyglucose... rubidium Rb-82	-	National Cancer Institute (NCI)
Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage	NCT05168839	Colorectal Canc...	FLUO+ : Intraop...	18 Years -	Centre Hospitalier Universitaire de Besancon
Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage	NCT05168839	Colorectal Canc...	FLUO+ : Intraop...	18 Years -	Centre Hospitalier Universitaire de Besancon
A Study of Perfusion of Colorectal Anastomosis Using FLuorescence AnGiography (FLAG-trial)	NCT03390517	Rectal Cancer Sigmoid Cancer	Fluorescence an...	18 Years -	State Scientific Centre of Coloproctology, Russian Federation

Spots Global Cancer Trial Database for fluorescence angiography