Visualization Of Ureters Research Articles

Utility and challenges of ureteral visualization using a fluorescent ureteral catheter in high risk surgeries for colorectal cancer.

Ureteral injury occurs in 0.3-1.5% of colorectal cancer surgeries. Devices to visualize the ureteral course and avoid ureteral injury are required for minimally invasive surgery (MIS). The NIRC™ fluorescent ureteral catheter (FUC) is a versatile ureteral visualization device currently available in Japan that can be used in combination with a variety of laparoscopic and robotic systems. In this study, we examined the outcomes of high-risk patients who underwent colorectal cancer surgery with FUC insertion. One hundred forty-one patients who underwent MIS for colorectal cancer and colorectal cancer recurrence at our institute between January 2021 and May 2024 underwent preoperative FUC insertion because of the high risk of ureteral injury and surgical difficulty. For these patients, patient background data and short-term outcomes were examined. The results are expressed as the median and interquartile range. Age, 70 [60-78]; M:F(n), 84:57; BMI, 22.1 [19.7-24.7]; T4 (TNM classification), 52 cases (36.9%); preoperative intestinal obstruction, 45 cases (31.9%); abscess formation, 30 cases (21%); surgical history, 70 cases (50%); recurrent cancer, 14 cases (9.9%); preoperative chemo-radiotherapy, 28 cases (19.9%); time required for FUC insertion, 12 [9-19] minutes; operation time, 412 [309-552] minutes; blood loss, 10 [5-30]ml; open conversion, 0 cases; postoperative hospitalization, 12 [9-17.5]; circumferential resection margins < 1mm (rectal surgery), 4/87 cases (4.6%); comorbidities, 0 ureteral injury, 1 urethral injury during FUC insertion (0.7%) and 16 CD Grade 3 or higher cases (11%). FUC may improve the safety of MIS and reduce blood loss in addition to preventing ureteral injury and is expected to have oncological advantages for ensuring the margin of the tumor without fear of ureteral injury. However, the time required for and complications associated with FUC are challenging. New methods for less invasive and easier ureteral visualization may be needed.

Intraoperative Fluorescent Ureter Visualization for Transvaginal High Uterosacral Ligament Suspension for Severe Pelvic Organ Prolapse.

We aimed to demonstrate the feasibility of ureteral navigation using intra-ureteric indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during transvaginal high uterosacral ligament suspension for prolapse repair to reduce the risk of iatrogenic ureteral injury. A cystoscope was inserted into the bladder, the tip of a 6-F open-end ureteral catheter was inserted into the ureteral orifices, and ICG was instilled into the ureters. The ureteral path was then clearly identified using NIRF imaging. Sutures were safely placed in the uterosacral ligaments at the level of the ischial spine, taking advantage of direct ureteral visualization. At the end of the procedure, diagnostic cystoscopy was performed to confirm ureteral patency. No intraoperative or postoperative complications were observed. Intra-ureteric ICG-NIRF imaging represents a simple, inexpensive, and reproducible trick for intraoperative ureteral detection, and could reassure surgeons during difficult operations, for instance, in the case of severe prolapse and/or when ureteral course abnormalities are expected.

Methodology of ICG marking technique in modern pelvic surgery: applied aspects (Literature review)

The article is devoted to a review of scientific publications on the use of the Indocyanine green (ICG) labeling technique in modern pelvic surgery. This dye was developed by Kodak Research Laboratories in 1955 and approved for clinical use in 1959, but has only recently come into widespread use. ICG-enhanced near-infrared fluorescence is introduced to improve visualization and provide more detailed anatomical localization during surgery.The dye binds to blood plasma proteins, it is quickly excreted from the organism and is non-toxic and has no found complications after its administration. Many studies have been conducted on the use of this technique: visualization of sentinel lymph nodes (SLN) in various oncogynecological diseases; visualization of ureters, lymphatic drainage, tissue perfusion, vessels of various sizes, colorectal blood circulation, etc. The high detection rate of SLN (unilateral and bilateral) with ICG compared with other dyes such as radiocolloid and patent blue suggests its effectiveness.The condition of SLN has an important prognostic and therapeutic value, based on the obtained results, a more correct further adjuvant treatment can be prescribed. A sentinel lymph node labeling procedure was performed as an alternative to systemic lymphadenectomy to assess the status of lymphovascular invasion. The use of ICG-marking allows to reduce the risk of intraoperative and postoperative complications. Many experimental studies have been conducted in relation to the assessment of uterine vascularization, preservation of individual vessels, their identification and measurement of blood flow.The article provides data from scientists on the use of the ICG-marking technique in endometrial, cervical, vulva, vaginal, ovarian cancer, as well as in endometriosis and for visualization of the ureters. This technique causes active discussions in the scientific community, requires further research and should be more widely used in various directions of surgical interventions.

Population Pharmacokinetic Modeling and Simulation of Pudexacianinium (ASP5354) for Dose Setting of a Phase 2 First-in-Patient Study: A Novel Imaging Agent for Intraoperative Ureter Visualization during Abdominopelvic Surgery.

Pudexacianinium (ASP5354) chloride is an indocyanine green derivative designed to enable enhanced ureter visualization during surgery. The objective of the present analysis was to determine appropriate doses of pudexacianinium for a phase 2, dose-ranging study (NCT04238481). Real-time urine pudexacianinium concentration is considered a good pharmacodynamic surrogate marker, since ureter visualization likely depends on its concentration in the ureter. Using plasma and urine concentrations of pudexacianinium from a phase 1 single-ascending-dose (0.1-24.0mg) study in healthy participants, a 3-compartment population pharmacokinetic model with a urine output compartment was developed and effectively described the concentration-time profiles. The individual estimated glomerular filtration rates had a significant impact on drug clearance. Simulations suggested that a 1.0mg intravenous injection would achieve target urine concentrations over 1μg/mL (determined from previous nonclinical studies) for 3 hours postdose, assuming a urine production rate of 1.0mL/min. Based on this simulation, doses of 0.3, 1.0, and 3.0mg were proposed for the phase 2 study. The observed plasma concentrations were generally consistent with model predictions. For urine, although only limited data could be obtained due to the difficulties of spot urine collection from surgical patients, intraoperative ureter visualization was successful at 1.0 and 3.0mg.

Pudexacianinium (ASP5354) chloride for ureter visualization in participants undergoing laparoscopic, minimally invasive colorectal surgery

BackgroundIntraoperative ureteral injury, a serious complication of abdominopelvic surgeries, can be avoided through ureter visualization. Near-infrared fluorescence imaging offers real-time anatomical visualization of ureters during surgery. Pudexacianinium (ASP5354) chloride is an indocyanine green derivative under investigation for intraoperative ureter visualization during colorectal or gynecologic surgery in adult and pediatric patients.MethodsIn this phase 2 study (NCT04238481), adults undergoing laparoscopic colorectal surgery were randomized to receive one intravenous dose of pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg. The primary endpoint was successful intraoperative ureter visualization, defined as observation of ureter fluorescence 30 min after pudexacianinium administration and at end of surgery. Safety and pharmacokinetics were also assessed.ResultsParticipants received pudexacianinium 0.3 mg (n = 3), 1.0 mg (n = 6), or 3.0 mg (n = 3). Most participants were female (n = 10; 83.3%); median age was 54 years (range 24–69) and median BMI was 29.3 kg/m2 (range 18.7–38.1). Successful intraoperative ureter visualization occurred in 2/3, 5/6, and 3/3 participants who received pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg, respectively. Median intensity values per surgeon assessment were 1 (mild) with the 0.3-mg dose, 2 (moderate) with the 1.0-mg dose, and 3 (strong) with the 3.0-mg dose. A correlation was observed between qualitative (surgeon’s recognition/identification of the ureter during surgery) and quantitative (video recordings of the surgeries after study completion) assessment of fluorescence intensity. Two participants experienced serious adverse events, none of which were drug-related toxicities. One adverse event (grade 1 proteinuria) was related to pudexacianinium. Plasma pudexacianinium concentrations were dose-dependent and the mean (± SD) percent excreted into urine during surgery was 22.3% ± 8.0% (0.3-mg dose), 15.6% ± 10.0% (1.0-mg dose), and 39.5% ± 12.4% (3.0-mg dose).ConclusionsIn this study, 1.0 and 3.0 mg pudexacianinium provided ureteral visualization for the duration of minimally invasive, laparoscopic colorectal procedures and was safe and well tolerated.

Simultaneous fluorescence imaging of bowel perfusion and ureter delineation using methylene blue: a demonstration in a porcine model

BackgroundIntraoperative near-infrared fluorescence imaging (NIRF) with preoperative optical dye administration is a promising technique for quick and easy intraoperative visualization of the ureter and for an improved, real-time assessment of intestinal perfusion. During colorectal surgery, there is a need for simultaneous non-invasive ureteral imaging and bowel perfusion assessment, using one single camera system. The purpose of this study is to investigate the feasibility of simultaneous intestinal perfusion and ureteral imaging using a single commercially available NIRF imaging system.MethodsSix Landrace pigs underwent laparotomy under general anesthesia in this experiment. An intravenous (IV) dose of 0.2 mg/kg indocyanine green (ICG) was given to assess bowel perfusion. Two pairs received a methylene blue (MB) iv injection of 0.75, 0.50 or 0.25 mg/kg respectively to investigate ureteral visualization. Quest Spectrum Fluorescence Camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging.ResultsUreter visualization and bowel perfusion under NIRF imaging was achieved in all animals. All ureters were visible after five to ten minutes and remained clearly visible until the end of every experiment (120–420 min). A mixed model analysis did not show any significant differences neither between the three groups nor over time. Importantly, we demonstrated that bowel perfusion could be visualized with methylene blue (MB) as well. We observed no interference between ICG and MB and a faster washout of MB.ConclusionWe successfully demonstrated simultaneous fluorescence angiography with ICG and ureteral imaging with MB in the same surgical procedure, with the same commercially available NIRF imaging equipment. More importantly, we showed that the use MB is adequate for bowel perfusion assessment and ureter visualization with this NIRF imaging system. Besides, MB showed an earlier washout time, which can be clinical beneficial as a repeated dye injection may be necessary during a surgical procedure.

Intravenous infusion of methylene blue to visualize the ureter in laparoscopic colorectal surgery

Objective: Intraoperative localization of the ureter can contribute to accurate dissection and minimize ureteral injury in colorectal surgery. We aim to summarize a single center's experience of fluorescence ureteral visualization using methylene blue (MB) and explore its visualization efficiency. Methods: This is a descriptive case-series-study. Clinical data of patients who had undergone laparoscopic colorectal surgery and fluorescence visualization of the ureter in the Gastrointestinal Surgery Department of Guangdong Provincial People's Hospital from March 2022 to May 2022 were retrospectively collected. Patients with incomplete surgery videos, renal insufficiency, or allergic reactions were excluded. MB was infused with 0.9% NaCl at 1.0 mg/kg in 100 mL of normal saline for 5 to 15 minutes during laparoscopic exploration. Imaging was performed using a device developed in-house by OptoMedic (Guangdong, China) that operates at 660nm to achieve excitation of MB. Clinical information, MB dosage, rate of successful fluorescence, time to fluorescence, operation time, blood loss, intraoperative blood oxygen levels, pathological staging, changes in renal function, and post-operative complications were retrospectively analyzed. Results: The study cohort comprised 27 patients (24 men and 3 women) with an average age of (60.25±16.95) years and an average body mass index of (21.72±3.42) kg/m2. The dosage of MB was 0.3-1.0 mg/kg and the infusion time was 5-15 minutes. Fluorescence signals were detected in all patients. The median time to signal detection was 20 (range, 10 to 40) minutes after MB infusion. The range of intraoperative blood oxygen fluctuation averaged 2.5% (range, 0 to 7.0%). The median change in creatine concentration was -1.3 (range, -17.2 to 29.2) µmol/L. No patients had complications associated with use of MB. Fluorescence visualization of the ureter was very valuable clinically in two patients (thick mesentery, stage T4). Conclusion: MB is a safe and effective means of visualizing the ureter by fluorescence during laparoscopic colorectal surgery, especially when the procedure is difficult. MB in a dosage of less than 1 mg/kg can slowly infused for more than 5 minutes during laparoscopic exploration. During the infusion, attention must be paid to blood oxygen fluctuations.

The Use of near Infra-Red Radiation Imaging after Injection of Indocyanine Green (NIR-ICG) during Laparoscopic Treatment of Benign Gynecologic Conditions: Towards Minimalized Surgery. A Systematic Review of Literature.

Background and Objectives: To assess the use of near infrared radiation imaging after injection of indocyanine green (NIR–ICG) during laparoscopic treatment of benign gynecologic conditions. Materials and Methods: A systematic review of the literature was performed searching 7 electronic databases from their inception to March 2022 for all studies which assessed the use of NIR–ICG during laparoscopic treatment of benign gynecological conditions. Results: 16 studies (1 randomized within subject clinical trial and 15 observational studies) with 416 women were included. Thirteen studies assessed patients with endometriosis, and 3 studies assessed non-endometriosis patients. In endometriosis patients, NIR–ICG use appeared to be a safe tool for improving the visualization of endometriotic lesions and ureters, the surgical decision-making process with the assessment of ureteral perfusion after conservative surgery and the intraoperative assessment of bowel perfusion during recto-sigmoid endometriosis nodule surgery. In non-endometriosis patients, NIR–ICG use appeared to be a safe tool for evaluating vascular perfusion of the vaginal cuff during total laparoscopic hysterectomy (TLH) and robotic-assisted total laparoscopic hysterectomy (RATLH), and intraoperative assessment of ovarian perfusion in adnexal torsion. Conclusions: NIR–ICG appeared to be a useful tool for enhancing laparoscopic treatment of some benign gynecologic conditions and for moving from minimally invasive surgery to minimalized surgery. In particular, it might improve treatment of endometriosis (with particular regard to deep infiltrating endometriosis), benign diseases requiring TLH and RATLH and adnexal torsion. However, although preliminary findings appear promising, further investigation with well-designed larger studies is needed.

EDITORIAL COMMENT

Prophylactic perioperative open-ended ureteral stent placement is commonly performed prior to major pelvic and abdominal surgery. Several retrospective studies and a recent meta-analysis including 98,507 patients have not demonstrated a clear difference in the risk of ureteral injury among stented versus unstented patients (OR 1.30, 95% CI 0.39-4.29).1 However these studies are highly subject to selection bias. Many surgeons believe that prophylactic stenting can ease intraoperative ureteral visualization and early identification of injuries, and they continue to request stents in select cases.

Comparison of static-fluid or excretory magnetic resonance urography with computed tomography urography for visualization of nondilated renal pelvises and ureters in healthy Beagles.

To assess the usefulness of magnetic resonance urography (MRU) for the visualization of nondilated renal pelvises and ureters in dogs and to compare our findings for MRU versus CT urography (CTU). 9 healthy Beagles. Dogs underwent CTU, static-fluid MRU, and excretory MRU, with ≥ 7 days between procedures. Contrast medium was administered IV during CTU and excretory MRU, whereas urine in the urinary tract was an intrinsic contrast medium for static-fluid MRU. For each procedure, furosemide (1 mg/kg, IV) was administered, and reconstructed dorsal plane images were acquired 3 minutes (n = 2) and 7 minutes (2) later. Images were scored for visualization of those structures and for image quality, diameters of renal pelvises and ureters were measured, and results were compared across imaging techniques. Excretory MRU and CTU allowed good visualization of the renal pelvises and ureters, whereas static-fluid MRU provided lower visualization of the ureters. Distention of the renal pelvises and ureters was good in excretory MRU and CTU. Distention of the ureters in static-fluid MRU was insufficient compared with that in CTU and excretory MRU. Distinct artifacts were not observed in CTU and excretory MRU images. Static-fluid MRU images had several mild motion artifacts. Our findings indicated that excretory MRU with furosemide administration was useful for visualizing nondilated renal pelvises and ureters of dogs in the present study. When performing MRU for the evaluation of dogs without urinary tract dilation, excretory MRU may be more suitable than static-fluid MRU.

Ureter identification utilizing indocyanine green (ICG) imaging in colorectal surgery: a systematic review of the literature

Aim: To describe the currently available evidence regarding the efficacy and safety of intraureteral indocyanine green (ICG) instillation for ureteral identification in colorectal surgery. Methods: Systematic search of PubMed and Scopus through May 2022 reported according to PRISMA 2020. Studies reporting treatment of patients &lt; 18 years, with unavailable full-text, reviews, editorials, animal studies, and studies including non-colorectal operations were excluded. Results: Seven retrospective studies, published between 2020 and 2022, were identified, in which 142 patients (43% females) were evaluated, of which three were undertaken in the USA, two in Japan, and two in India. The most common indications for surgery were cancer in 58 patients (41%) and diverticular disease in 52 patients (36.6%). Most patients involved underwent robotic surgery (70%), while the remaining patients had laparoscopic surgery. The intraoperative ureteral injury was reported in one patient, while adverse effects (mainly transient hematuria) were reported in 10% of the study population (14 patients). The use of intrauretal ICG prolonged surgery by a median of 12.8 minutes. Conclusion: Intraoperative visualization of ureters using ICG in colorectal surgery is safe and effective, according to the results of this study. However, this technique still bears the potential disadvantages of ureteral catheterization. Research is focusing on future dyes combining the ICG properties with renal excretion to minimize the need for stents. Further comparative studies are needed to reach safe results.

Feasibility of injected indocyanine green for ureteral identification during robotic left-sided colorectal resections

BackgroundUreteral identification is essential to performing safe colorectal surgery. Injected immunofluorescence may aid with ureteral identification, but feasibility without ureteral catheterization is not well described. MethodsCase series of robotic colorectal resections where indocyanine green (ICG) injection with or without ureteral catheter placement was performed. Imaging protocol, time to ureteral identification, and factors impacting visualization are reported. ResultsFrom 2019 to 2020, 83 patients underwent ureteral ICG injection, 20 with catheterization and 63 with injection only. Main indications were diverticulitis (52%) and cancer (36%). Median time to instill ICG was faster with injection alone than with catheter placement (4min vs 13.5min, p < 0.001). Median time [IQR] to right ureter (0.3 [0.01–1.2] min after robot docking) and left ureter (5.5 [3.1–8.8] min after beginning dissection) visualization was not different between injection alone and catheterization. ConclusionICG injection alone is faster than with indwelling catheter placement and equally reliable at intraoperative ureteral identification.

Preclinical Development and Validation of ASP5354: A Near-Infrared Fluorescent Agent for Intraoperative Ureter Visualization.

Iatrogenic ureteral injury (IUI) can complicate minimally invasive and open abdominopelvic surgery. The incidence of IUI is low and dependent on the type of surgery (< 10 %), but it is associated with high morbidity. Therefore, intraoperative visualization of the ureter is critical to reduce the incidence of IUI, and some methodologies for ureter visualization have been developed. Amongst these, near-infrared fluorescence (NIRF) visualization is thought to bring an advantage with real-time retroperitoneal visualization through the retroperitoneum. We investigated an indocyanine green (ICG) derivative, ASP5354, which emits NIRF at 820 nm when exposed to near-infrared light at a wavelength of 780 nm, in a rodent and porcine model. Wistar rats and Göttingen minipigs under anesthesia were laparotomized and then administered ASP5354 chloride intravenously at dose of 0.03 and 0.3 mg/kg for rats and 0.001 and 0.01 mg/kg for minipigs, respectively. Videos of the abdominal cavity in minipigs were taken using a near-infrared fluorescent camera (pde-neo) and assessed visually by three independent clinicians. Toxicological evaluation was demonstrated with cynomolgus monkeys. The proportion of animals whose ureters were visible up to 3 h after administration of ASP5354 chloride were 33 % at 0.001 mg/kg and 100 % at 0.01 mg/kg, respectively. In a toxicological study in cynomolgus monkeys, ASP5354 chloride demonstrated no significant toxicity, suggesting that 0.01 mg/kg provides an optimal dose when used clinically and could allow for ureter visualization during routine surgical procedures. The dose of 0.01 mg/kg provided an optimal dose for ureter visualization up to 3 h after administration. ASP5354 shows promise for ureter visualization during abdominopelvic surgery, which may potentially lower the risk of IUI.

Intraoperative ureter identification with a novel fluorescent catheter

Iatrogenic ureteral injuries (IUI) occur in 0.5–1.3% of cases during abdominal surgery. If not recognized intraoperatively, IUI increase morbidity/mortality. A universally accepted method to prevent IUI is lacking. Near-infrared fluorescent imaging (NIRF), penetrating deeper than normal light within the tissue, might be useful, therefore ureter visualization combining NIRF with special dyes (i.e. IRDye 800BK) is promising. Aim of this work is to evaluate the detection of ureters using stents coated with a novel biocompatible fluorescent material (NICE: near-infrared coating of equipment), during laparoscopy. female pigs underwent placement of NICE-coated stents (NS). NIRF was performed, and fluorescence intensity (FI) was computed. Successively, 0.15 mg/kg of IRDye 800BK was administered intravenously, and FI was computed at different timepoints. Ureter visualization using NS only was further assessed in a human cadaver. Both methods allowed in vivo ureter visualization, with equal FI. However, NS were constantly visible whereas IRDye 800BK allowed visualization exclusively during the ureteral peristaltic phases. In the human cadaver, NS provided excellent ureter visualization in its natural anatomical position. NS provided continuous ureteral visualization with similar FI as the IRDye 800BK, which exclusively allowed intermittent visualization, dependent on ureteral peristalsis. NS might prove useful to visualize ureters intraoperatively, potentially preventing IUI.

Assessment of distal ureteral and ureterovesical junction visualization on contrast-enhanced voiding urosonography.

Contrast-enhanced voiding urosonography (CEVUS) uses intravesically administered microbubble contrast to detect vesicoureteral reflux (VUR) and urethral anomalies with ultrasound. Multiple studies have suggested CEVUS can replace voiding cystourethrogram (VCUG) as a radiation-free alternative. Analysis of the ureterovesical junction and ureters on VCUG documenting the ureterovesical junction position, ureteral duplication, periureteral diverticula and ureteroceles is important as anatomical variations may affect management and surgical approach. Our purpose was to assess distal ureteral and ureterovesical junction region visualization in children with VUR detected on CEVUS. CEVUS studies performed between June 2018 and March 2019 with reported VUR were retrospectively reviewed by two pediatric radiologists to confirm VUR and to qualitatively assess the ureterovesical junction region for each renal moiety using a 3-point scale for clear, limited or absent visualization of the distal ureter, ureterovesical junction, ureteral duplication, periureteral diverticula and ureteroceles. Thirty-four studies with VUR on CEVUS were identified. Sixty-seven renal moieties were evaluated including a solitary kidney in one child. VUR was detected in 52 moieties by reader 1 and in 53 by reader 2. A single moiety with discrepancy between readers regarding VUR was excluded from statistical analysis. No diverticula were detected by either reader and one ureterocele was detected by both readers. Visualization of the ureterovesical junction was described as clear in 5/52, limited in 14/52 and absent in 33/52 refluxing renal moieties by reader 1 and as clear in 12/52, limited in 20/52 and absent in 20/52 by reader 2. The ureterovesical junction was clearly visualized in 5/52 (9.6%) by reader 1 and 12/52 (23.1%) by reader 2. The Kappa value of -0.29 (confidence interval [CI] -0.25, 0.21) reveals a lack of agreement between the readers for clear versus limited or absent ureterovesical junction visualization. Distal ureteral visualization was described as clear in 14/52, limited in 16/52 and absent in 22/52 refluxing renal moieties by reader 1 and as clear in 27/52, limited in 7/52 and absent in 18/52 by reader 2. The distal ureter was clearly visualized in 14/52 (26.9%) by reader 1 and 27/52 (51.9%) by reader 2. The Kappa of 0.43 (CI 0.22, 0.64) reveals moderate agreement between the readers for clear versus limited or absent distal ureteral visualization. Duplication of the renal collecting system was identified in 13/52 refluxing kidneys by reader 1 and 11/52 refluxing kidneys by reader 2. Visualization of ureteral duplication was described as clear in 9, limited in 4 and absent in 39 of 52 refluxing renal moieties by reader 1 and as clear in 9, limited in 2 and absent in 41 by reader 2. Ureteral duplication was clearly visualized in 9/52 (17.3%) by reader 1 and 9/52 (17.3%) by reader 2. Kappa of 0.87 (CI 0.68, 1) reveals high agreement between the readers for clear versus limited or absent identification of ureteral duplication. The distal ureter and ureterovesical junction region frequently are not clearly visualized in refluxing renal moieties on CEVUS. Awareness of this limitation is important as there may be implications when evaluating patients for surgical management of VUR.

A systematic review of clinically available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters during laparoscopic surgery

Background: Iatrogenic ureteral injury is a rare but serious complication during laparoscopic abdominopelvic surgery. Preoperative ureteral stent placement can facilitate intraoperative identification of the ureters. However, even with ureteral stents, visualization of ureters during laparoscopic abdominopelvic surgery can be challenging due to their retroperitoneal location and, particularly during robot-assisted surgery, the lack of tactile feedback. Recently, the use of near-infrared (NIR) fluorescence imaging showed to be a good non-invasive alternative for intraoperative ureter identification. The aim of this review is to provide an overview of current clinically available contrast agents for NIR fluorescence imaging of the ureters during laparoscopic surgery and also focuses on novel experimental dyes.

Intraureteral indocyanine green augments ureteral identification and avoidance during complex robotic-assisted colorectal surgery.

Up to 10% of patients who undergo nonurological abdominopelvic operations suffer a ureteral injury. While preoperative ureteral stenting to facilitate identification of the ureter is common, it does not reduce the incidence of intraoperative ureteral injury and is not without risk. As we continue to broaden the application of minimally invasive surgical techniques, a new form of ureteral identification and avoidance that does not rely on tactile feedback is needed. We report our initial experience with intraureteral indocyanine green (ICG) for ureteral identification and avoidance during complex robotic-assisted colorectal surgery. Patients undergoing adjunctive ureteral identification during robotic-assisted colorectal surgery were prospectively identified. Each patient underwent intraureteral ICG administration using rigid cystoscopy (22 Fr). A 5-Fr open-ended ureteral catheter was inserted up to 20cm and used to inject 5ml of 2.5mg/ml ICG as the catheter was withdrawn to the ureteral orifice. Intraureteral ICG was then detected using near-infrared laser fluorescence technology (Firefly®). Successful ICG-enhanced ureteral identification and avoidance was performed in 15 of 16 (94%) patients undergoing robotic-assisted colorectal surgery. The median ICG instillation time was 11.5min (range 4-21min) and the median operative time with ICG visualization was 489min (8h 9min) [range 268-738min (4h 28min-12h 18min)]. No patient experienced intraoperative ureteral injury and there were no adverse sequelae or complications associated with intraureteral ICG administration. Intraureteral ICG is a safe and effective method of intraoperative ureteral identification and avoidance during complex robotic-assisted colorectal surgery. Precise and prolonged ureteral visualization was achieved, allowing for long operative times compatible with complex robotic-assisted operations.

Methylene Blue-Current Knowledge, Fluorescent Properties, and Its Future Use.

Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its’ function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.

Utility of Intraoperative Fluorescence Imaging in Gynecologic Surgery: Systematic Review and Consensus Statement.

This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery. A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations. Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery. For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.

Noninvasive Near-Infrared Fluorescence Imaging of the Ureter During Robotic Surgery: A Demonstration in a Porcine Model.

Background: Iatrogenic ureteral injury is one of the feared complications during intrapelvic surgery. There are limited data on the use of novel near-infrared fluorescence (NIRF) imaging dyes for the purpose of noninvasive ureteral visualization in robot-assisted laparoscopic surgery (RALS). In this study, we evaluated the feasibility of NIRF imaging of the ureter using the IRDye® 800BK dye as the fluorescence dye and a robotic platform with Firefly™ technology as an imaging system. Materials and Methods: An intravenous dose of 0.15 mg/kg was administered in 3 pigs and NIRF imaging was performed for a total duration of 60 minutes. The intraoperative video recordings were analyzed to determine fluorescence intensities and the target-to-background ratio (TBR). Results: In all included animals, a clear delineation of the ureter was achieved from 5 minutes after dye administration until the end of the study. During this time period, the ureter was clearly distinguishable from its surroundings and no statistical differences in TBR were observed. Conclusion: The IRDye 800BK dye, a novel NIRF dye currently undergoing clinical translation, is a promising contrast agent used for noninvasive ureteral imaging, which has the potential to be valuable during RALS.