Cholecystitis, Hepatocellular Carcinoma, Liver Metastases
Conditions
Keywords
Biliary Tract, Indocyanine Green (ICG), Tumors, Near-infrared Fluorescence
Brief summary
Near-infrared fluorescence (NIRF) imaging after an intravenous injection of indocyanine green (ICG) allows for the intraoperative identification of liver anatomy. The investigators have new data that a much lower dose improves this visualization. Confirmation of this hypothesis would mean that ICG can be administered on the same day of surgery in order to augment real-time intraoperative visualization, thereby providing a safe, feasible, and cost-effective strategy for the surgical treatment of liver disease.
Detailed description
The investigators have a series of surgical cases in which the investigators have been able to achieve excellent intraoperative biliary visualization with a greatly decreased (50-200 fold lower) dose of ICG than the previously published dose. Furthermore, this decreased dose was visible in about 15-20 minutes from the time of injection with low liver background fluorescence, a significant improvement that would make its utilization in the operating room more practical. The investigators hypothesize that a lower dose will: 1) allow adequate visualization of the extrahepatic biliary tree, including the cystic, common hepatic, and common bile ducts. Confirmation of hypotheses would mean that a lower dose of ICG can be administered on the same day of surgery in order to augment real-time intraoperative localization of the extrahepatic biliary tree, thereby providing a safe, feasible, and cost-effective strategy for the surgical treatment of liver disease. The investigators intend to test our hypothesis with the following specific aims: Aim 1: To compare the efficacy and utility of a low dose ICG (0.05 mg) protocol with a previously published dose (2.5 mg) in imaging the extrahepatic biliary tract.
Interventions
DRUGIndocyanine green
Low dose or standard dose ICG will be administered by the anesthesiologist as guided by the study coordinator at the beginning of the case, at two points during the operation (1- prior to the dissection of the biliary tract and 2- upon completion of the dissection and establishment of the critical view of safety).
DEVICEPINPOINT Endoscopic Fluorescence
The PINPOINT Endoscopic Fluorescence Imaging System (Stryker Corporation, Kalamazoo, Michigan) will be used. This device enables the surgeon to simultaneously see real-time, high-definition visible-range and NIR fluorescence videos and to superimpose them. It is currently approved by the FDA for intraoperative near-infrared fluorescence imaging.
Sponsors
Society of University Surgeons
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Masking description
To mask the investigator randomization will be done with envelopes for this study and the dose given to the patient prior to surgery with the investigator not being aware of the amount given.
Intervention model description
Adult patients scheduled to undergo a laparoscopic hepatic or biliary operation will be randomized to two groups 1) low dose (0.05 mg) or 2) standard dose (2.5 mg) of ICG preoperatively on the day of surgery. Patients with a history of adverse reactions or known allergy to ICG, iodine, or iodine dyes will be excluded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing standard of care laparoscopic hepatic or biliary operations or Patients undergoing standard of care laparoscopic resection for hepatic tumors: hepatocellular carcinoma or metastatic tumor
Exclusion criteria
* Patients with a history of adverse reactions or known allergy to ICG, iodine, or iodine dyes and Pregnant and/or lactating patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio | intraoperative, average of 2 hours | Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the liver |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree - NIRFC Versus White Light | intraoperative, average of 2 hours | A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations). |
| Quantitative Assessment - Bile Duct-to-background Fat Fluorescence Intensity Ratio | intraoperative, average of 2 hours | Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the background fat |
| Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | intraoperative, average of 2 hours | A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations). |
Countries
United States
Participant flow
Recruitment details
Patients undergoing a planned laparoscopic cholecystectomy were approached between September 2021 to August 2022 in pre-surgical clinic and consented for a randomized ICG dose administration.
Pre-assignment details
No enrolled patients were excluded from the study prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Prior to surgery these patients will be given a ICG dose of 0.05 mg IV.
Indocyanine green: Low dose or standard dose ICG will be administered by the anesthesiologist as guided by the study coordinator at the beginning of the case, at two points during the operation (1- prior to the dissection of the biliary tract and 2- upon completion of the dissection and establishment of the critical view of safety). | 32 |
| Standard Dose Prior to surgery these patients will be given a ICG dose of 2.5 mg IV.
Indocyanine green: Low dose or standard dose ICG will be administered by the anesthesiologist as guided by the study coordinator at the beginning of the case, at two points during the operation (1- prior to the dissection of the biliary tract and 2- upon completion of the dissection and establishment of the critical view of safety). | 28 |
| Total | 60 |
Baseline characteristics
| Characteristic | Total | Low Dose | Standard Dose |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 6 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 26 Participants | 20 Participants |
| Age, Continuous | 57 years | 53 years | 60 years |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 8 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized White | 46 participants | 26 participants | 24 participants |
| Region of Enrollment United States | 60 participants | 32 participants | 28 participants |
| Sex: Female, Male Female | 45 Participants | 23 Participants | 22 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 26 |
| other Total, other adverse events | 0 / 29 | 0 / 26 |
| serious Total, serious adverse events | 0 / 29 | 0 / 26 |
Outcome results
Primary
Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio
Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the liver
Time frame: intraoperative, average of 2 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose | Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio | 2.7 ratio |
| Standard Dose | Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio | 0.7 ratio |
Secondary
Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts)
A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations).
Time frame: intraoperative, average of 2 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Common Hepatic Duct | 3.6 score on a scale | Standard Deviation 1.4 |
| Low Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Cystic Duct | 3.6 score on a scale | Standard Deviation 1.3 |
| Low Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Common Bile Duct | 3.6 score on a scale | Standard Deviation 1.3 |
| Low Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Aberrant Duct | 2.8 score on a scale | Standard Deviation 1.3 |
| Standard Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Aberrant Duct | 2.3 score on a scale | Standard Deviation 0.4 |
| Standard Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Common Hepatic Duct | 2.8 score on a scale | Standard Deviation 1.3 |
| Standard Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Common Bile Duct | 3.1 score on a scale | Standard Deviation 1.3 |
| Standard Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | Cystic Duct | 3.5 score on a scale | Standard Deviation 1.2 |
Secondary
Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree - NIRFC Versus White Light
A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations).
Time frame: intraoperative, average of 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree - NIRFC Versus White Light | 3.4 score on a scale | Standard Deviation 1.3 |
| Standard Dose | Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree - NIRFC Versus White Light | 3.1 score on a scale | Standard Deviation 1 |
Secondary
Quantitative Assessment - Bile Duct-to-background Fat Fluorescence Intensity Ratio
Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the background fat
Time frame: intraoperative, average of 2 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose | Quantitative Assessment - Bile Duct-to-background Fat Fluorescence Intensity Ratio | 6.1 ratio |
| Standard Dose | Quantitative Assessment - Bile Duct-to-background Fat Fluorescence Intensity Ratio | 2.7 ratio |