Near-infrared cholangiography with intragallbladder indocyanine green injection in minimally invasive cholecystectomy

Laparoscopic cholecystectomy(LC)remains one of the most commonly performed procedures in adult and paediatric populations.Despite the advances made in intraoperative biliary anatomy recognition,iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems.A series of methods have been proposed to prevent bile duct injury,among them the use of indocyanine green(ICG)fluorescence.The most commonly reported method of ICG injection is the intravenous administration,while literature is lacking studies investigating the direct intragallbladder ICG injection.This narrative mini-review aims to assess the potential applications,usefulness,and limitations of intragallbladder ICG fluorescence in LC.Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy,as well as special issues regarding its use.Literature search retrieved four prospective cohort studies,three case-control studies,and one case report.In the three case-control studies selected,intragallbladder near-infrared cholangiography(NIRC)was compared with standard LC under white light,with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography(IOC).In total,133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC.Literature includes several reports of intragallbladder ICG administration,but a standardized technique has not been established yet.Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping,overwhelming limitations of IOC including intervention and radiation exposure,as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence.Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.

Laparoscopic left hemihepatectomy guided by indocyanine green fluorescence: A cranial-dorsal approach

BACKGROUND Advancements in laparoscopic technology and a deeper understanding of intra-hepatic anatomy have led to the establishment of more precise laparoscopic hepatectomy(LH)techniques.The indocyanine green(ICG)fluorescence navi-gation technique has emerged as the most effective method for identifying hepatic regions,potentially overcoming the limitations of LH.While laparoscopic left hemihepatectomy(LLH)is a standardized procedure,there is a need for innova-tive strategies to enhance its outcomes.important anatomical markers,surgical skills,and ICG staining methods.METHODS Thirty-seven patients who underwent ICG fluorescence-guided LLH at Qujing Second People's Hospital between January 2019 and February 2022 were retrospectively analyzed.The cranial-dorsal approach was performed which involves dissecting the left hepatic vein cephalad,isolating the Arantius ligament,exposing the middle hepatic vein,and dissecting the parenchyma from the dorsal to the foot in order to complete the anatomical LLH.The surgical methods,as well as intra-and post-surgical data,were recorded and analyzed.Our hospital’s Medical Ethics Committee approved this study(Ethical review:2022-019-01).RESULTS Intraoperative blood loss during LLH was 335.68±99.869 mL and the rates of transfusion and conversion to laparotomy were 13.5%and 0%,respectively.The overall incidence of complications throughout the follow-up(median of 18 months;range 1-36 months)was 21.6%.No mortality or severe complications(level IV)were reported.CONCLUSION LLH has the potential to become a novel,standardized approach that can effectively,safely,and simply expose the middle hepatic vein and meet the requirements of precision surgery.

Pay attention to the application of indocyanine green fluorescence imaging technology in laparoscopic liver cancer resection

Traditional laparoscopic liver cancer resection faces challenges,such as difficultiesin tumor localization and accurate marking of liver segments,as well as theinability to provide real-time intraoperative navigation.This approach falls shortof meeting the demands for precise and anatomical liver resection.The introductionof fluorescence imaging technology,particularly indocyanine green,hasdemonstrated significant advantages in visualizing bile ducts,tumor localization,segment staining,microscopic lesion display,margin examination,and lymphnode visualization.This technology addresses the inherent limitations oftraditional laparoscopy,which lacks direct tactile feedback,and is increasinglybecoming the standard in laparoscopic procedures.Guided by fluorescenceimaging technology,laparoscopic liver cancer resection is poised to become thepredominant technique for liver tumor removal,enhancing the accuracy,safetyand efficiency of the procedure.

Don’t forget emergency surgery! Lessons to learn from elective indocyanine green-guided gastrointestinal interventions

Fluorescence-based imaging has found application in several fields of elective surgery,but there is still a lack of evidence in the literature about its use in the emergency setting.Clinical trials have consistently shown that indocyanine green(ICG)-guided surgery can dramatically reduce the risk of postoperative complic-ations,length of in-hospital stay and total healthcare costs in the elective setting.It is well-known that emergency surgery has a higher complication rate than its elective counterpart,therefore an impelling need for research studies to explore,validate and develop this issue has been highlighted.The present editorial aims to provide a critical overview of currently available applications and pitfalls of ICG fluorescence in abdominal emergencies.Furthermore,we evidenced how the experience of ICG-fluorescence in elective surgery might be of great help in implementing its use in acute situations.In the first paragraph we analyzed the tips and tricks of ICG-guided cancer surgery that might be exploited in acute cases.We then deepened the two most described topics in ICG-guided emergency surgery:Acute cholecystitis and intestinal ischemia,focusing on both the advantages and limitations of green-fluorescence application in these two fields.In emergency situations,ICG fluorescence demonstrates a promising role in preventing undue intestinal resections or their entity,facilitating the detection of intestinal ischemic zones,identifying biliary tree anatomy,reducing post-operative complications,and mitigating high mortality rates.The need to improve its application still exists,therefore we strongly believe that the elective and routinary use of the dye is the best way to acquire the necessary skills for emer-gency procedures.

Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis

BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology surgery.The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice.AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric cancer.METHODS Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy.Stata 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"command.The true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P<0.01 was considered to indicate statistical significance.A funnel plot was used to assess publication bias,and P<0.1 was considered to indicate statistical significance.The summary receiver operating characteristic(SROC)curve was used to calculate the area under the curve(AUC)to determine the diagnostic accuracy.If there was interstudy heterogeneity(I2>50%),meta-regression analysis and subgroup analysis were performed.analysis were performed.RESULTS Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis.The positive likelihood ratio was 30.39(95%CI:0.92-1.00),the sensitivity was 0.95(95%CI:0.82-0.99),and the specificity was 1.00(95%CI:0.92-1.00).The negative likelihood ratio was 0.05(95%CI:0.01-0.20),the diagnostic odds ratio was 225.54(95%CI:88.81-572.77),and the SROC AUC was 1.00(95%CI:The crucial values were sensitivity=0.95(95%CI:0.82-0.99)and specificity=1.00(95%CI:0.92-1.00).The Deeks method revealed that the"diagnostic odds ratio"funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical(P=0.01),suggesting significant publication bias.Further meta-subgroup analysis revealed that,compared with fluorescence imaging,NIR imaging had greater sensitivity(0.98 vs 0.73).Compared with optical imaging immediately after ICG injection,optical imaging after 20 minutes obtained greater sensitivity(0.98 vs 0.70).Compared with that of patients with an average SLN detection number<4,the sensitivity of patients with a SLN detection number≥4 was greater(0.96 vs 0.68).Compared with hematoxylin-eosin(HE)staining,immunohistochemical(+HE)staining showed greater sensitivity(0.99 vs 0.84).Compared with subserous injection of ICG,submucosal injection achieved greater sensitivity(0.98 vs 0.40).Compared with 5 g/L ICG,0.5 and 0.05 g/L ICG had greater sensitivity(0.98 vs 0.83),and cT1 stage had greater sensitivity(0.96 vs 0.72)than cT2 to cT3 clinical stage.Compared with that of patients≤26,the sensitivity of patients>26 was greater(0.96 vs 0.65).Compared with the literature published before 2010,the sensitivity of the literature published after 2010 was greater(0.97 vs 0.81),and the differences were statistically significant(all P<0.05).CONCLUSION For the diagnosis of stomach cancer,optical imaging in conjunction with ICG-guided SLN biopsy is a therapeut-ically viable approach,especially for early gastric cancer.The concentration of ICG used in the SLN biopsy of gastric cancer may be too high.Moreover,NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

Indocyanine green:The guide to safer and more effective surgery

In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal Surgery.The authors present an interesting review on the use of indocyanine green fluo-rescence in different aspects of abdominal surgery.They also highlight future perspectives of the use of indocyanine green in mini-invasive surgery.Indo-cyanine green,used for fluorescence imaging,has been approved by the Food and Drug Administration and is safe for use in humans.It can be administered in-travenously or intra-arterially.Since its advent,there have been several advance-ments in the applications of indocyanine green,especially in the surgical field,such as intraoperative mapping and biopsy of sentinel lymph node,measurement of hepatic function prior to resection,in neurosurgical cases to detect vascular anomalies,in cardiovascular cases for patency and assessment of vascular ab-normalities,in predicting healing following amputations,in helping visualization of hepatobiliary anatomy and blood vessels,in reconstructive surgery,to assess flap viability and for the evaluation of tissue perfusion following major trauma and burns.For these reasons,the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant surgery.Co-lorectal surgery has just lately begun to adopt this technique,particularly for perfusion visualization to prevent anastomotic leakage.The regular use of in-docyanine green coupled with fluorescence angiography has recently been pro-posed as a feasible tool to help improve patient outcomes.Using the best available data,it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic leak.The use of indocyanine green is proven to be safe,feasible,and effective in both elective and emergency scenarios.However,additional robust evidence from larger-scale,high-quality studies is essential before incorporating indocyanine green guided surgery into standard practice.

Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients

BACKGROUND Application of indocyanine green(ICG)fluorescence has led to new developments in gastrointestinal surgery.However,little is known about the use of ICG for the diagnosis of postoperative gut leakage(GL).In addition,there is a lack of rapid and intuitive methods to definitively diagnose postoperative GL.AIM To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery patients.METHODS Sixteen rats were divided into two groups:GL group(n=8)and sham group(n=8).Approximately 0.5 mL of ICG(2.5 mg/mL)was intravenously injected postoperatively.The peritoneal fluid was collected for the fluorescence test at 24 and 48 h.Six patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG(2.5 mg/mL)on postoperative day 1.Their ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy stoma.Participants who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic test.The peritoneal fluids from drainage were collected 24 h after ICG injection.The ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging system.RESULTS The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham group.Six samples of ostomy fluids showed green fluorescence,indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in patients.The peritoneal fluid ICG test exhibited a sensitivity of 100%and a specificity of 83.3%for the diagnosis of GL.The positive predictive value was 71.4%,while the negative predictive value was 100%.The likelihood ratios were 6.0 for a positive test result and 0 for a negative result.CONCLUSION The postoperative ICG test in a drainage tube is a valuable and simple technique for the diagnosis of GL.Hence,it should be employed in clinical settings in patients with suspected GL.

Indocyanine green plasma clearance rate and 99mTc-galactosyl human serum albumin single-photon emission computed tomography evaluated preoperative remnant liver

BACKGROUND Preoperative evaluation of future remnant liver reserves is important for safe hepatectomy.If the remnant is small,preoperative portal vein embolization(PVE)is useful.Liver volume analysis has been the primary method of preoperative evaluation,although functional examination may be more accurate.We have used the functional evaluation liver using the indocyanine green plasma clearance rate(KICG)and 99mTc-galactosyl human serum albumin single-photon emission computed tomography(99mTc-GSA SPECT)for safe hepatectomy.AIM To analyze the safety of our institution’s system for evaluating the remnant liver reserve.METHODS We retrospectively reviewed the records of 23 patients who underwent preoperative PVE.Two types of remnant liver KICG were defined as follows:Anatomical volume remnant KICG(a-rem-KICG),determined as the remnant liver anatomical volume rate×KICG;and functional volume remnant KICG(frem-KICG),determined as the remnant liver functional volume rate based on 99mTc-GSA SPECT×KICG.If either of the remnant liver KICGs were>0.05,a hepatectomy was performed.Perioperative factors were analyzed.We defined the marginal group as patients with a-rem-KICG of<0.05 and a f-rem-KICG of>0.05 and compared the postoperative outcomes between the marginal and not marginal(both a-rem-KICG and f-rem-KICG>0.05)groups.RESULTS All 23 patients underwent planned hepatectomies.Right hepatectomy,right trisectionectomy and left trisectionectomy were in 16,6 and 1 cases,respectively.The mean of blood loss and operative time were 576 mL and 474 min,respectively.The increased amount of frem-KICG was significantly larger than that of a-rem-KICG after PVE(0.034 vs 0.012,P=0.0273).The not marginal and marginal groups had 17(73.9%)and 6(26.1%)patients,respectively.The complications of Clavian-Dindo classification grade II or higher and post-hepatectomy liver failure were observed in six(26.1%)and one(grade A,4.3%)patient,respectively.The 90-d mortality was zero.The marginal group had no significant difference in postoperative outcomes(prothrombin time/international normalised ratio,total bilirubin,complication,post-hepatectomy liver failure,hospital stay,90-d,and mortality)compared with the not-marginal group.CONCLUSION Functional evaluation of the remnant liver enabled safe hepatectomy and may extend the indication for hepatectomy after PVE treatment.

indocyanine green-based fluorescence imaging in visceral and hepatobiliary and pancreatic surgery:State of the art and future directions

In recent years, the use of fluorescence-guided surgery(FGS) to treat benign and malignant visceral, hepatobiliary and pancreatic neoplasms has significantly increased. FGS relies on the fluorescence signal emitted by injected substances(fluorophores) after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible. This review surveys and discusses the most common and emerging clinical applications of indocyanine green(ICG)-based fluorescence in visceral, hepatobiliary and pancreatic surgery. The analysis, findings, and discussion presented here rely on the authors' significant experience with this technique in their medical institutions, an up-to-date review of the most relevant articles published on this topic between 2014 and 2018, and lengthy discussions with key opinion leaders in the field during recent conferences and congresses. For each application, the benefits and limitations of this technique, as well as applicable future directions, are described. The imaging of fluorescence emitted by ICG is a simple, fast,relatively inexpensive, and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems. The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future. Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis

BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R(15)) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R(15) and MELD score increased. There were significant statistical differences in K value, R(15) and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R(15)) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P < 0.05), while a positive correlation was observed between R(15) and MELD score (r=0.804, P < 0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R(15) have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory.The indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis.In addition, the MELD scores and KCH criteria were calculated.RESULTS: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-0.4686), with a significant difference between the two groups(χ2=25.307, P=0.000).CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the shortterm prognosis of patients with ALF.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

Comparison of sentinel lymph node detection performances using blue dye in conjunction with indocyanine green or radioisotope in breast cancer patients: a prospective singlecenter randomized study

Objective:This randomized study aimed to compare the clinical efficacy between the novel dual tracer composed of indocyanine green(ICG)and blue dye(BD)and the conventional dual tracer composed of radioisotope and BD for sentinel lymph node(SLN)mapping in patients with breast cancer.Methods:This study enrolled 471 clinically lymph node-negative patients with primary breast cancer.All patients underwent mastectomy,and those undergoing sentinel lymph node biopsy(SLNB)were randomized to receive blue dye plus radioisotope(RB group)or BD plus ICG(IB group).The detection performances on SLN identification rate,positive SLN counts,detection sensitivity,and false-negative rate were compared between the two groups.Results:In the IB group,97%(194/200)of the patients who underwent the ICG and BD dual tracer injection showed fluorescentpositive lymphatic vessels within 2–5 min.The identification rate of SLNs was comparable between the IB group(99.0%,198/200)and the RB group(99.6%,270/271)(P=0.79).No significant differences were observed in the identification rate of metastatic SLNs(22.5%vs.22.9%,P>0.05,RB group vs.IB group,the same below),positive SLN counts(3.72±2.28 vs.3.91±2.13,P>0.05),positive metastatic SLN counts(0.38±0.84 vs.0.34±0.78,P>0.05),SLNB detection sensitivity(94.4%vs.92.5%,P>0.05),or false-negative rate(5.6%vs.7.5%,P>0.05)between the two groups.Conclusions:ICG can be used as a promising alternative tracer for radioisotope in SLN mapping,and when it is combined with BD in lymphangiography,it offers comparable detection sensitivity compared to the conventional lymphatic mapping strategies that are widely used in clinical practice.

Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer

BACKGROUND As one effective treatment for lateral pelvic lymph node(LPLN)metastasis(LPNM),laparoscopic LPLN dissection(LPND)is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery.With regard to improving the accuracy and completeness of LPND as well as safety,we tried an innovative method using indocyanine green(ICG)visualized with a near-infrared(NIR)camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.AIM To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.METHODS A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision(TME)and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group.Clinical characteristics,operative outcomes,pathological outcomes,and postoperative complication information were compared and analysed between the two groups.RESULTS Compared to the non-ICG group,the ICG group had significantly lower intraoperative blood loss(55.8±37.5 mL vs 108.0±52.7 mL,P=0.003)and a significantly larger number of LPLNs harvested(11.5±5.9 vs 7.1±4.8,P=0.017).The LPLNs of two patients in the non-IVG group were residual during LPND.In addition,no significant difference was found in terms of LPND,LPNM,operative time,conversion to laparotomy,preoperative complication,or hospital stay(P>0.05).CONCLUSION ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.

Indocyanine Green Nanoparticles for Theranostic Applications

Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.

Rapid measurement of indocyanine green retention by pulse spectrophotometry: a validation study in 70 patients with Child-Pugh A cirrhosis before hepatectomy for hepatocellular carcinoma

BACKGROUND: The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly- developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON , one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method. METHODS: We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L)). RESULTS: The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16×ICGR15(L)+2.73.CONCLUSIONS: The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula.

Indocyanine green clearance in evaluating the recovery of liver reserve function after superselective transarterial chemoembolization

Transarterial chemoembolization(TACE)may ravage normal liver tissues apart from the neoplastic nodules which offset the anti-tumor effect.This study aimed to evaluate the recovery of liver reserve function(LRF)after TACE by indocyanine green(ICG)clearance test and other routine liver function tests.Forty-six newly diagnosed HCC patients who had undergone TACE as the initial treatment from January 2011 to January 2012 were enrolled in this study.The effects of age,basic ICG clearance rate and interval time between two assessments on the recovery of LRF were analyzed.We found that ICG retention rate at the 15 minutes(ICGR15)was significantly increased after TACE(12.3±8.1%vs 16.8±12.1%,P【0.01)in all the 46 patients.In particular,the ICGR15 value was increased in older patients(age】55 years,20.3±12.5%vs 13.7±7.2%,P【0.01).The interval of ICG test also affected the ICGR15 value(≤47days,17.8±11.4%after vs 12.1±7.1%before TACE,P【0.01).Our data suggested that TACE decreased LRF,especially in older patients.ICG test was more sensitive to evaluate the recovery of LRF after TACE than the Child-Pugh grade and routine liver function tests.

Added value of indocyanine green fluorescence imaging in liver surgery

Recently,indocyanine green(ICG)fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery,to detect hepatic tumors,for accurate anatomical hepatectomy,and to increase the safety and accuracy of minimally invasive(laparoscopic and robotic)hepatectomy.The clinical relevance of this method has been increasing gradually,as new procedures develop in this field.Various important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.

Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: The state of the art

Indocyanine green(ICG)fluorescence imaging is widely used in abdominal surgery.The implementation of minimally invasive rectal surgery using new methods like robotics or a transanal approach required improvement of optical systems.In that setting,ICG fluorescence optimizes intraoperative vision of anatomical structures by improving blood and lymphatic flow.The purpose of this review was to summarize all potential applications of this upcoming technology in rectal cancer surgery.Each type of use has been separately addressed and the evidence was investigated.During rectal resection,ICG fluorescence angiography is mainly used to evaluate the perfusion of the colonic stump in order to reduce the risk of anastomotic leaks.In addition,ICG fluorescence imaging allows easy visualization of organs such as the ureter or urethra to protect them from injury.This intraoperative technology is a valuable tool for conducting lymph node dissection along the iliac lymphatic chain or to better identifying the rectal dissection planes when a transanal approach is performed.This is an overview of the applications of ICG fluorescence imaging in current surgical practice and a synthesis of the results obtained from the literature.Although further studies are need to investigate the real clinical benefits,these findings may enhance use of ICG fluorescence in current clinical practice and stimulate future research on new applications.