Prediction of Survival After Partial Hepatectomy Using a Physiologically Based Pharmacokinetic Model of Indocyanine Green Liver Function Tests

The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology as well as in hepatobiliary surgery. Indocyanine green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of hepatectomy are how liver disease such as cirrhosis alters ICG elimination, and if postoperative survival can be predicted from preoperative ICG measurements. Within this work a physiologically based pharmacokinetic (PBPK) model of ICG was developed and applied to the prediction of the effects of a liver resection under various degrees of cirrhosis. For the parametrization of the computational model and validation of model predictions a database of ICG pharmacokinetic data was established.

The model was applied

(i) to study the effect of liver cirrhosis and liver resection on ICG pharmacokinetics; and
(ii) to evaluate the model-based prediction of postoperative ICG-R15 (retention ratio 15 min after administration) as a measure for postoperative outcome. Key results are the accurate prediction of changes in ICG pharmacokinetics caused by liver cirrhosis and postoperative changes of ICG-elimination after liver resection, as validated with a wide range of data sets. Based on the PBPK model, individual survival after liver resection could be classified, demonstrating its potential value as a clinical tool.

https://www.frontiersin.org/articles/10.3389/fphys.2021.730418/full#B52

The Applications of 3D Imaging and Indocyanine Green Dye Fluorescence in Laparoscopic Liver Surgery

Laparoscopic liver resections have gained widespread popularity among hepatobiliary surgeons and is nowadays performed for both standard and more complex hepatectomies. Given the increased technical challenges, preoperative planning and intraoperative guidance is pivotal in laparoscopic surgery to safely carry out complex and oncologically safe hepatectomies. Indocyanine green retention dye is an increasingly used tool that can nowadays improve the precision during laparoscopic hepatectomies, especially when considering anatomical resection. The use of preoperative modern imaging and intraoperative indocyanine green dye are key to successfully perform complex hepatectomies such as laparoscopic parenchymal sparing liver resections.

Technological advancements in liver surgery have allowed to increase the preoperative knowledge of the patient’s anatomy and plan the procedure accordingly. Preoperative 3D imaging and reconstructions, 3D printing and ICG guided surgery are tools that are increasingly used in experienced hepatobiliary centers. In modern laparoscopic liver surgery, these technological improvements allow to tailor the procedure to the specific patient and disease, minimizing the chance of postoperative events meanwhile ensuring a safe and oncologically sound resection.

https://www.mdpi.com/2075-4418/11/12/2169/pdf

Polypoidal Choroidal Vasculopathy Diagnosis and Neovascular Activity Evaluation Using Optical Coherence Tomography Angiography

Purpose: To examine choroidal neovascularization (CNV) characteristics in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), using swept-source optical coherence tomography angiography (SS-OCTA), and investigate agreement with OCT B-scan, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) by two different examiners.

Results: A total of 27 patients (11 females (40.7%) and 16 males (59.3%), P = 0.231) were included in the analysis. Among those, 13 patients presented with neovascular AMD and 14 patients with PCV. There were 92.3% of correct answers regarding appropriate diagnosis and lesion characterization among AMD patients, against 61.5% of correct answers among PCV patients. The overall interrater reliability agreement between examiners, using Cohen’s kappa coefficient (κ) was 0.70 (0.5082-0.8916). Disagreement was found with one active AMD misdiagnosed as inactive AMD, three inactive PCV misdiagnosed as inactive AMD, and one inactive PCV misdiagnosed as active AMD.

Conclusion: SS-OCTA alone remains limited in some specific phenotypes of PCV, which suggests the ongoing role of B-scan OCT associated with FFA and ICGA in the diagnosis of these conditions.

https://pubmed.ncbi.nlm.nih.gov/34825001/

The Role of Indocyanine Green Fluorescence Angiography in Complex Abdominal Wall Reconstruction: A Scoping Review of the Literature

Indocyanine green fluorescence angiography (ICGFA) is a technique for assessing vascularity and perfusion which has multiple proven applications across a variety of surgical procedures. Studies have been performed assessing its potential role in evaluating skin flap viability in complex abdominal wall reconstruction (CAWR) in order to avoid postoperative surgical site occurrences (SSO).  This scoping review was intended to summarise the literature concerning ICGFA in CAWR in order to facilitate future evidence-based guidelines for its use.

RESULTS: A total of 3416 unique titles were yielded from our search of which 9 met our inclusion criteria: 3 case reports, 1 retrospective case series, 1 prospective case series, 3 non-blinded, non-randomised retrospective case-controlled studies and 1 prospective, double-blinded randomised controlled study. The included studies varied considerably in size and method however the consensus appeared to support ICGFA as being a safe and feasible means of assessing tissue flap vascularity in CAWR. The studies returned contrasting results regarding the impact of ICGFA in predicting and avoiding SSOs however there were insufficient numbers of studies for a meta-analysis. Evidence-based guidelines on the role of ICGFA in CAWR will require the assessment of further studies.

https://pubmed.ncbi.nlm.nih.gov/34753685/

Morphological and Functional Relationship Between OCTA and FA/ICGA Quantitative Features in AMD-Related Macular Neovascularization

Background: The aim was to study the relationship between quantitative information provided by optical coherence tomography (OCT) angiography (OCTA) and conventional angiography in macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).

Methods: The research was designed as an interventional, prospective study. We included 66 eyes (66 patients) affected by naïve MNV. Multimodal imaging included structural OCT, OCTA, fluorescein angiography (FA), and indocyanine green angiography (ICGA). The follow-up lasted 1 year. Patients were treated by PRN anti-VEGF injections. Based on FA/ICGA examinations, we divided the patients into two categories: low vessel tortuosity (VT) (<8.40) and high VT (>8.40), correlating VT with the MNV area, leakage area, speckled fluorescence (SF) quadrants and MNV area/leakage area ratio.

Results: Mean baseline BCVA was 0.50 ± 0.61 LogMAR, improved to 0.31 ± 0.29 LogMAR after 1 year (p < 0.01), with a mean number of 7 ± 2 anti-VEGF injections. The patients revealed type-1 MNV in 36 eyes (55%), mixed type 1 and 2 MNV in 18 eyes (27%), and type-2 MNV in 12 eyes (18%). MNV eyes in high-VT MNV featured poorer BCVA, CMT, and OCTA parameters, higher SF quadrants, and less exudation, compared with low-VT MNV (p < 0.01). Moreover, 30% of high-VT MNV eyes developed outer retinal atrophy.

The strength of this new quantitative approach is that it offers an estimate of MNV activity, thus providing useful information about the evolution of the neovascular lesion and the damage caused to retinal structures. However, from the point of view of its association with the functional features of the MNV, the methodology fails to provide an assessment of the relationship between the information supplied by OCTA and data obtained from dye-based angiography. In particular, OCTA is well-known to yield little regarding the blood-retinal barrier breakdown and the exudative phenomena, which are, in contrast, well detected by dye-based angiography.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564015/

Indocyanine green: An old drug with novel applications

Indocyanine green (ICG), a US Food and Drug Administration-approved fluorescent compound, has been on the medical stage for more than 60 years. Current uses include hepatic function evaluation before surgical procedure and fundus evaluation. The large safety margin and near-infrared fluorescent optical advantage of the drug have proved useful in several clinical trials of intraoperative systems for tumor removal. Several nanoparticle-sized formulations for thermal ablation and photodynamic therapy have also been evaluated in animal experiments. Studies have attempted to manipulate ICG as a reporter fluorophore with initial success. In this article, we reviewed ICG’s histological applications, chemical and physical properties, current clinical applications, ongoing clinical trials, and biomedical studies and prospects. We believe that ICG could be used with novel biotechnological techniques, such as fluorescent endoscopy and photoacoustic equipment, in a range of biomedical fields.

https://pubmed.ncbi.nlm.nih.gov/34760625/

Use of indocyanine green fluorescence guidance in redo ileocolic resection for Crohn’s disease. Paper published by Michael R Freund, Ilan Kent, Samir Agarwal, Steven D Wexner

Background: Redo ileocolic resection in patients with Crohn’s disease (CD) is associated with significant technical challenges that may be associated with high complication rates. We aimed to evaluate the feasibility of near infra-red fluorescence angiography with indocyanine green (ICG), often used to evaluate blood supply to the anastomosis in CD patients undergoing repeat ileocolic resection.

Methods: A retrospective analysis of patients who underwent redo ileocolic resection using ICG bowel perfusion assessment during 2015-2021 were matched and compared on a 1:2 basis to a control group undergoing the same procedure without perfusion assessment.

Results: 12 patients underwent redo ileocolic resection with ICG perfusion assessment (ICG group) and compared to 24 patients who underwent the procedure without ICG (control group). Both groups were similar in demographics and operative characteristics including median operating time (255 vs 255.5 minutes, p=0.39) and conversion rate (22% vs 36.8%, p=0.68). Median estimated blood loss was significantly higher in the ICG group [150 (50-400) vs 100 ml (20-125)]. Successful ICG perfusion assessment was seen in all patients in the ICG group and did not change management in any case. Overall postoperative complication rates were comparable between the groups (58.3% vs. 54.1%, p=0.72). No anastomotic leaks occurred in the ICG group compared to one patient (1/24, 4.2%) in the control group (p=0.99).

Conclusions: Fluorescence ICG perfusion assessment is feasible and safe in redo ileocolic resection in CD patients. Larger studies are needed to evaluate whether this technique should be routinely used in these complex surgical interventions.

https://pubmed.ncbi.nlm.nih.gov/34741391/

The Impact of Indocyanine Green Fluorescence Angiography on Intraoperative Decision Making in Right Hemicolectomy: A Case-Control Study

Introduction: Anastomotic leak (AL) after right hemicolectomy remains a significant clinical challenge with an incidence of 4.2% to 8.2% in European series. Near infrared imaging with indocyanine green (NIR-ICG) allows real-time assessment of bowel perfusion. However, there is a lack of published data assessing the clinical utility of this new technology in right sided colonic resection.

Results: Our study included 127 patients, with 65 in the NIR-ICG group and 62 in the control group. Median length of follow-up was 24 months. There was no significant difference in demographic or pathologic characteristics between the 2 cohorts. There was no significant difference in operation length between the NIR-ICG and control groups (164.7 vs. 162.9 min, P=0.88). The use of NIR-ICG altered the intraoperative course in 4/65 (6.2%) patients. The rate of AL was lower in the NIR-ICG group (1.5% vs. 4.8%), although this did not reach statistical significance.

Conclusion: The use of NIR-ICG altered the intraoperative course for notable subset of patients undergoing right hemicolectomy without prolonging operative time. Larger prospective studies are required to evaluate the potential for the routine use of this technology to reduce AL rate in right hemicolectomy.

https://pubmed.ncbi.nlm.nih.gov/34739425/

Comparison of Various Modalities Utilized for Preoperative Planning in Microsurgical Reconstructive Surgery

The benefits of preoperative perforator imaging for microsurgical reconstruction have been well established in the literature. An extensive literature review was performed to determine the most commonly used modalities, and their applicability, advantages and disadvantages.

Results: The review demonstrated various findings including decreases in operative time and cost with the use of CT angiography to identification of perforators for inclusion in flap design with hand-held Doppler ultrasound. Modalities like MR angiography offer alternatives for patients with contrast allergies or renal dysfunction while maintaining a high level of clarity and fidelity. Although the use of conventional angiography has decreased due to the availability of less invasive alternatives, it continues to serve a role in the preoperative evaluation of patients for lower extremity reconstruction. Duplex ultrasonography has been of great interest recently as an inexpensive, risk free, and extraordinarily accurate diagnostic tool. Emerging technologies such as indocyanine green fluorescence angiography and dynamic infrared thermography provide real-time information about tissue vascularity and perfusion without requiring radiation exposure.

https://pubmed.ncbi.nlm.nih.gov/34688218/

Laparoscopic Posterolateral Sectionectomy in Hepatocellular Cacinoma – Increasing Oncological Precision by Combining the Glissonean Pedicle Approach and Fluorescence Guidance

Aim: Minimally invasive procedures have been increasingly performed in liver surgery. Benefits include lower intraoperative blood loss, reduced postoperative morbidity and shorter lengths of hospital stay in comparison to open liver surgery. Exact resection margins seem advantageous in primary liver cancer but challenging to implement with minimally invasive techniques. In this case report, we aimed to increase surgical precision by combining the Glissonean pedicle approach and intraoperative fluorescence guidance.

Indication: A 73-year-old female patient with CHILD A liver cirrhosis with chronic hepatitis C virus infection was transferred to our hospital with high levels of alpha-fetoprotein (792 ng/ml). Sectional imaging confirmed the suspected diagnosis of a single hepatocellular carcinoma (HCC) with a size of 2.2 cm in segments VI/VII. In line with the local tumour board recommendation, an anatomical posterolateral sectionectomy using the Glissonean pedicle approach was planned.

After mobilisation of the right liver, the posterolateral pedicle was encircled and transected. 0.2 mg/kg of body mass indocyanine green (ICG) was then injected intravenously. The perfused parenchyma of segments I-V and VIII turned green, but the unperfused posterolateral segment VI and VII remained native. The transection line was marked under ICG-imaging to indicate the transition of the posterolateral to the anteromedial sector. Parenchymal transection was performed under intermittent ICG-guided imaging. Pathological workup confirmed R0 resection of a well differentiated HCC in a cirrhotic liver (grade 4). The patient was discharged from the hospital on the 6th postoperative day after an uncomplicated course and was confirmed to be tumour-free six months after surgery.

Conclusion: As an additional intraoperative tool, ICG-imaging may provide visualisation of segment and sector boundaries and thus may enable precise anatomical resection. Prospective studies are needed to evaluate the added value of this technique, especially with regard to the rate of R0 resections.

https://pubmed.ncbi.nlm.nih.gov/34706376/