Indocyanine Green Clearance Research Articles

Value of contrast-enhanced ultrasound for preoperative assessment of liver reserve function in patients with liver tumors.

This study aimed to investigate the value of contrast-enhanced ultrasound (CEUS) for preoperative assessment of liver reserve function in patients with liver tumors. The indocyanine green (ICG) clearance tests and CEUS examinations of 45 noncirrhotic patients with liver tumors were performed prior to liver resection. Parameters time to peak (TtoPk), arrival time (Atm) as well as perfusion parameters A, k and A x k were generated from time-intensity curve (TIC) of CEUS. The correlation analyses of the ICG clearance per unit time (ICGK) and the retention rate at 15 min (ICGR15) with TtoPk, Atm, A, k and A x k were performed, and the diagnostic ability as well as optimal cut-off values of TtoPk and Atm for differentiating patients with ICGR15>10% from ICGR15<10% were analyzed. There were significant correlations of ICGK with TtoPk and Atm, and the correlation coefficients were 0.363 (p = 0.014) and -0.482 (p = 0.001), respectively. Significant correlations of ICGR15 with TtoPk and Atm were revealed, and the correlation coefficients were -0.416 (p = 0.004) and 0.303 (p = 0.043), respectively. No correlation of ICGK or ICGR15 with A, k and A x k was found in this study. There were significant differences in TtoPk and Atm between patients with ICGR15>10% and ICGR15<10% (p = 0.028 and p = 0.026, respectively). TtoPk and Atm both had good diagnostic abilities in diagnosing patients with ICGR15>10% verusus ICGR15<10% (AUROC = 0.711 and 0.721, respectively). For ICGR15>10% vs ICGR15, the optimal cut-off values of TtoPk and Atm were 13.307 s and 11.007 s, respectively, while the sensitivity and specificity were 75.0% and 72.7%, 60.6% and 75.0%, respectively. This study revealed that CEUS has the potential to be a new method to evaluate the liver reserve function of patients. With the optimal cut-off values of TtoPk and Atm, qualitative assessment of patients with ICGR15>10% could be more easily achieved by CEUS with good diagnostic abilities.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery

Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Indocyanine green clearance of remnant liver (ICG-Krem) predicts postoperative subclinical hepatic insufficiency after resection of colorectal liver metastasis: theoretical validation for safe expansion of Makuuchi's criteria

BackgroundMultidisciplinary treatment for colorectal liver metastases (CLMs) often includes major hepatectomy for preoperative chemotherapy-related hepatic injury, although the safety limit for resection extent is unclear. We investigated this parameter using the estimated indocyanine green clearance rate (ICG-K) of liver remnants, focusing on postoperative subclinical hepatic insufficiency (PHI). MethodsAltogether, 225 patients who underwent resection of CLMs were studied. The predictive power of estimated ICG-K of liver remnant (ICG-Krem) for subclinical PHI (peak bilirubin ≥3 mg/dL or refractory ascites) was compared with those of other potential predictors. The suggested safety limit of ICG-Krem ≥0.05 was also assessed. ResultsReceiver-operating curve analysis revealed that ICG-Krem [area under the curve (AUC) 0.752, cutoff 0.102] was the best predictor of subclinical PHI (AUC range for others was 0.632–0.668). Makuuchi's criteria corresponded to ICG-Krem 0.10. Subclinical PHI incidence was significantly elevated at ICG-Krem <0.10 (26% vs 8%, p = 0.002), while potentially fatal PHI (peak bilirubin >7 mg/dL) was not observed until down to ICG-Krem of 0.05. ConclusionsICG-Krem sensitively predicts subclinical PHI. Liver failure-related death could be avoided so long as ICG-Krem remains at ≥0.05. However, patients with ICG-Krem 0.05–0.10 are at high risk of subclinical PHI and require intensive care postoperatively.

Predictive Value of Intraoperative Indocyanine Green Clearance Measurement on Postoperative Liver Function After Anatomic Major Liver Resection

BackgroundThe aim of this study was to evaluate the predictive value of measuring indocyanine green (ICG) clearance during intraoperative partial occlusion of liver lobes to be resected on postoperative liver function following major anatomic liver resection. MethodsWe prospectively included 46 patients, and 35 patients ultimately underwent anatomic major liver resection. ICG clearance was measured preoperatively and intraoperatively. Intraoperative ICG clearance was measured immediately after selective occlusion of hepatic arterial, portal, and hepatic venous blood flow to the liver lobes to be resected. The albumin-bilirubin (ALBI) grade, albumin-indocyanine green evaluation (ALICE) grade, platelet count, remnant liver volume per kilogram of weight (RLV/kg), and future liver remnant plasma clearance rate of ICG (ICGK-FLR) were measured preoperatively. ResultsAn intraoperative ICG retention at 15 min (I-R15) greater than 13.8% indicates transient posthepatectomy liver failure (PHLF) and Clavien-Dindo > grade I complications. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) for predicting PHLF and Clavien-Dindo > grade I complications was 0.797 and 0.734, respectively (p = 0.001 and 0.014). Furthermore, an I-R15 greater than 22.7% indicates mid-term PHLF, and the AUC was 0.911 (p < 0.0001). The I-R15 is a better predictor of PHLF than the ALBI grade, ALICE grade, platelet count, RLV/kg, and ICGK-FLR. ConclusionsIntraoperative ICG clearance measurements during partial occlusion of blood flow accurately predict postoperative liver function and could be new criteria for determining the feasibility and safety of anatomic major liver resection.

The value of indocyanine green clearance assessment to predict postoperative liver dysfunction in patients undergoing liver resection

Postoperative liver dysfunction remains a major concern following hepatic resection. In order to identify patients who are at risk of developing liver dysfunction, indocyanine green (ICG) clearance has been proposed to predict postoperative liver function. All patients who underwent liver resection at the Medical University Vienna, Austria between 2006 and 2015 with preoperative ICG clearance testing (PDR, R15) were analyzed in this study. Postoperative liver dysfunction was analyzed as defined by the International Study Group of Liver Surgery. Overall, 698 patients (male: 394 (56.4%); female: 304 (43.6%)) with a mean age of 61.3 years (SD: 12.9) were included in this study, including 313 minor liver resections (44.8%) and 385 major liver resections (55.2%). One hundred and seven patients developed postoperative liver dysfunction after liver resection (15.3%). Factors associated with liver dysfunction were: male sex (p = 0.043), major liver resection (p < 0.0001), and preoperative ICG clearance (PDR (p = 0.002) and R15 (p < 0.0001)). Notably ICG clearance was significantly associated with liver dysfunction in minor and major liver resections respectively and remained a predictor upon multivariable analysis. An optimal cut-off for preoperative ICG clearance to accurately predict liver dysfunction was PDR < 19.5%/min and R15 > 5.6%. To the best of our knowledge, this is the largest study analyzing the predictive value of preoperative ICG clearance assessment in patients undergoing liver resection. ICG clearance is useful to identify patients at risk of postoperative liver dysfunction.

Pulsed Laser Diode-Based Desktop Photoacoustic Tomography for Monitoring Wash-In and Wash-Out of Dye in Rat Cortical Vasculature.

Photoacoustic (PA) tomography (PAT) imaging is an emerging biomedical imaging modality useful in various preclinical and clinical applications. Custom-made circular ring array-based transducers and conventional bulky Nd:YAG/OPO lasers inhibit translation of the PAT system to clinics. Ultra-compact pulsed laser diodes (PLDs) are currently being used as an alternative source of near-infrared excitation for PA imaging. High-speed dynamic in vivo imaging has been demonstrated using a compact PLD-based desktop PAT system (PLD-PAT). A visualized experimental protocol using the desktop PLD-PAT system is provided in this work for dynamic in vivo brain imaging. The protocol describes the desktop PLD-PAT system configuration, preparation of animal for brain vascular imaging, and procedure for dynamic visualization of indocyanine green (ICG) dye uptake and clearance process in rat cortical vasculature.

Clearance of Indocyanine Green in Severe Pediatric Burns.

Clearance of indocyanine green dye (ICGc) reflects sinusoidal perfusion and hepatocyte cell membrane function. Thus, ICGc is a reflection of the functional reserve of intact hepatocytes. The purpose of this study was to identify predictors of ICGc in severely burned children during the acute hospitalization and at the time of discharge from the intensive care unit (ICU). A secondary aim was to determine the relationship between liver size and patient ICGc. Twenty-six children (0.8-17 years old) with 35% or greater total body surface area burned (%TBSA-B) were included. Assessment of ICGc (in milliliters per minute per meter squared) was done during the acute hospitalization (median: 6 days after admission, median: 14 days postburn) and at the time of discharge from the ICU (median: 19 days after admission, median: 27 days postburn). Age, TBSA-B, % third-degree burns, inhalation injury, preexisting chronic malnutrition, hematocrit, liver dysfunction, and time from burn injury were incorporated in multiple linear regressions as predictive variables of ICGc. Only variables with p < 0.05 were retained in the final models. Time from injury and age were the strongest predictors of ICGc during the acute admission but not at the time of discharge from the ICU. Time from injury was negatively associated with ICGc, whereas age was positively associated. At the time of discharge from the ICU, ICGc was increased in proportion to the %TBSA-B, whereas inhalation injury and preexisting chronic malnutrition were associated with lower ICGc. There was no correlation between change-to-predicted liver length and ICGc. The intrinsic ability of the liver to extract ICG from plasma was lower in younger burned patients during the acute admission and in those with preexisting chronic malnutrition and inhalation injury at the time of discharge from the ICU. Prognostic/Epidemiologic, level III.

Does Ct volumetry accurately predict functional reserve of the future liver remnant after major hepatectomy?

Background: Precise quantitative tests are not available to measure synthetic liver function prior to major hepatectomy. Most centers rely on imperfect surrogates including laboratory studies and CT volumetry. Indocyanine green clearance can quantify functional hepatocyte mass, but does not provide regional assessment and has not been widely adopted in North America. Nuclear medicine tests are rarely used for preoperative planning, but are an additional option to asses overall, hemi-liver, and segmental hepatic function. The purpose of this study was to compare CT volumetry with functional nuclear medicine testing as an accurate measure to predict hepatic function of the future liver remnant. Methods: CT volumetry and functional nuclear medicine data were collected prospectively for patients undergoing evaluation for hepatocellular carcinoma (HCC) from February 2016-May 2018. Paired CT and nuclear medicine scans were obtained within 9 months (median 1 month) of one another. Nuclear medicine scans were performed with freshly prepared technetium 99m labeled mebrofenin (an iminodiacetic analogue), initially dynamic planar images were acquired and thereafter a single-photon emission computed tomography (SPECT) scan was performed. Total and regional liver volumes were calculated and reported by an attending radiologist. Extent of discrepancy between modalities was calculated. Clinical and demographic characteristics including the extent of chronic liver disease were recorded. Results: Over 27 months, 63 patients with HCC underwent both CT and functional nuclear medicine imaging. Median age was 64 years (range 25–85 yrs). Fifty patients (74.6%) were classified as cirrhotic. Of the cirrhotic patients, 60% (n = 30) had Child’s A, 38% Child's B (n = 19) and 2% Child's C cirrhosis (n = 1). Standard CT volumetry overestimated total functional liver volume, TLV, (median 1508 ml; range 570.2–4112.9 ml) when compared with functional nuclear medicine scan (median 1320 ml; range 6.9–3546.1 ml; p = 0.02). Significant discrepancy existed between regional liver volumes and percent contribution to hepatic function. The median volume of the right hemi-liver by CT volumetry was 906 ml (range 187–2324; 61% of TLV) and 721 ml by functional nuclear medicine study (range 12–2050; 65% of TLV; p = 0.03). Less discrepancy was found between left hemi-liver measurements: median volume by CT volumetry was 591 ml (range 100–2236; 38% of TLV) and 512 ml by functional nuclear medicine scan (range 69–2050; 35% of TLV; p = 0.21). Median discrepancy in hemi-liver volumes was 4.8% (range 0.2–51.5%) for the right, and 4.7% (0.2–51.5%) for the left hemi-liver. More than half of the patients (n = 34) had less than 5% discrepancy in hemi-liver volumes, 10 had 5–10% discrepancy, 11 had 10–20% discrepancy. Eight patients (12%) had volume discrepancies greater than 20% between CT volumetry and nuclear medicine imaging. Conclusion: Significant discrepancy exists between standard CT volumetry and nuclear medicine SPECT for estimating functional liver volumes. Compared with functional nuclear medicine imaging, CT volumetry appears to overestimate liver volume. Functional nuclear medicine scans provide additional information and may be a useful and affordable tool for preoperative assessment of the future liver remnant when planning major hepatectomy.

Expanded Makuuchi's criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection

BackgroundRecent advances in liver surgery have dramatically improved the safety of hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes for patients fulfilling an extended criteria vs. those fulfilling the conventional criteria based on the bilirubin and indocyanine green (ICG) clearance (Makuuchi's criteria). MethodsThe short term outcomes of patients undergoing hepatectomy for HCC and who fulfilled the expanded criteria (ICG clearance of future remnant liver [ICG-Krem] ≥ 0.05 estimated using 3-D volumetry) were retrospectively reviewed and were compared between those fulfilling the conventional criteria. Postoperative hepatic insufficiency (PHI) was defined as peak total bilirubin >7 mg/dL. ResultsA total of 323 patients undergoing resection of whom 269 (83%) met conventional criteria (In-M) and 54 (17%) extended criteria (Ex-M). The overall morbidity rates were not significantly different. The incidence of PHI was 0.37% in In-M and 3.7% in Ex-M (P = 0.074), with no liver-related deaths. When the ICG-Krem ≥ 0.05 criterion was included, major hepatectomy was performed in 24 patients (41%) in Ex-M with no significant increase in major morbidity (13%), PHI(3.3%), or liver-related death (0%) compared with minor hepatectomy (n = 30) in Ex-M(10%, 4% and 0%, respectively). ConclusionsObjective criteria using ICG clearance rate and 3-D volumetry may offer opportunities for safe surgical resection in selected patients exceeding the conventional criteria.

Infrared imaging of lymphatic function in the upper extremity of normal controls and hand transplant recipients via subcutaneous indocyanine green injection

Objectives:The goal of this study was to define the parameters of movement of indocyanine green in the upper extremity of normal control and hand transplant recipients. The purpose was to establish a non-invasive method of determining the level of lymphatic function in hand transplant recipients. In hand transplantation (and replantation), the deep lymphatic vessels are rarely repaired, resulting in altered lymphatic connections. In most cases, the relatively rapid inosculation of superficial lymphatic networks and drainage via the venous systems results in sufficient interstitial fluid and lymph drainage of the graft to prevent edema. However, our group and others have determined that some transplant recipients demonstrate chronic edema which is associated with lymphatic stasis. In one case, a patient with chronic edema has developed chronic rejection characterized by thinning of the skin, loss of adnexal structures, and fibrosis and contracture of the hand.Methods:Lymphatic function was evaluated by intradermal administration of near-infrared fluorescent dye, indocyanine green, and dynamic imaging with an infrared camera system (LUNA). To date, the assessment of lymphatic drainage in the upper extremity by clearance of indocyanine green dye has been studied primarily in oncology patients with abnormal lymphatic function, making assessment of normal drainage problematic. To establish normal parameters, indocyanine green lymphatic clearance functional tests were performed in a series of normal controls, and subsequently compared with indocyanine green clearance in hand transplant recipients.Results:The results demonstrate varied patterns of lymphatic drainage in the hand transplant patients that partially mimic normal hand lymphatic drainage, but also share characteristics of lymphedema patients defined in other studies. The study revealed significant deceleration of the dye drainage in the allograft of a patient with suspected chronic rejection and edema of the graft. Analysis of other hand transplant recipients revealed differing levels of dye deceleration, often localized at the level of surgical anastomosis.Conclusion:These studies suggest intradermal injection of indocyanine green and near-infrared imaging may be a useful clinical tool to assess adequacy of lymphatic function in hand transplant recipients.

Donor Risk Index Has an Impact in Intraoperative Measure of Hepatic Artery Flow and in Clearance of Indocyanine Green: An Observational Cohort Study

BackgroundThe increase in indications for liver transplantation has led to acceptance of donors with expanded criteria. The donor risk index (DRI) was validated with the aim of being a predictive model of graft survival based on donor characteristics. Intraoperative arterial hepatic flow and indocyanine green clearance (plasma clearance rate of indocyanine green [ICG-PDR]) are easily measurable variables in the intraoperative period that may be influenced by graft quality. Our aim was to analyze the influence of DRI on intraoperative liver hemodynamic alterations and on intraoperative dynamic liver function testing (ICG-PDR). MethodsThis investigation was an observational study of a single-center cohort (n = 228) with prospective data collection and retrospective data analysis. Measurement of intraoperative flow was made with a VeriQ flowmeter based on measurement of transit time (MFTT). The ICG-PDR was obtained from all patients with a LiMON monitor (Pulsion Medical Systems AG, Munich, Germany). DRI was calculated using a previously validated formula. Normally distributed variables were compared using Student's t test. Otherwise, the Mann-Whitney U test or Kruskal-Wallis test was applied, depending on whether there were 2 or more comparable groups. The qualitative variables and risk measurements were analyzed using the chi-square test. P < .05 was considered statistically significant. ResultsDRI score (mean ± SD) was 1.58 ± 0.31. The group with DRI >1.7 (poor quality) had an intraoperative arterial flow of 234.2 ± 121.35 mL/min compared with the group having DRI < 1.7 (high quality), with an intraoperative arterial flow of 287.24 ± 156.84 mL/min (P = .02). The group with DRI >1.70 had an ICG-PDR of 14.75 ± 6.52%/min at 60 minutes after reperfusion compared to the group with DRI <1.70, with an ICG-PDR of 16.68 ± 6.47%/min at 60 minutes after reperfusion (P = .09). ConclusionPoor quality grafts have greater susceptibility to ischemia-reperfusion damage. Decreased intraoperative hepatic arterial flow may represent an increase in intrahepatic resistance early in the intraoperative period.

Validation of liver function and prediction scoring system

Introduction: Liver resection is performed for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique and perioperative management, posthepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. To avoid PHLF, we used various examination such as ICGR15, KICG, and estimated ICGR15 and KICG which are estimated by 99mTc-GSA SPECT, and functional liver volume estimated by 99mTc-GSA SPECT/MDCT fusion image, and used various prediction scoring system such as Makuuchi’s criteria, Prediction Score made by Hyogo college of medicine (PS), and Indocyanine green clearance of the future remnant liver (remKICG). The present study aimed to identify the risk factors for PHLF and validate these prediction formulas. Method: 329 patients who underwent hepatectomy without extrahepatic bile duct resection were retrospectively analyzed. Among 329 patients, major hepatectomy was performed in 79 patients (24%). Grade B and C PHLF based on ISGLS definition occurred in 11 patients (3.3%). Univariate and multivariate analyses were performed to identify the risk factors for PHLF. Result: The functional resection volume rate estimated by 99mTc-GSA SPECT/MDCT fusion image (%FRV), direct bilirubin and KICG were the risk factors according to multivariate analysis. Functional remKICG calculated by using %FRV and KICG which were obtained by multivariate analysis, had a sensitivity of 18.2%, a specificity of 100%, a positive prediction value of 100%, and a negative prediction value of 97.2%. Conclusion: %FRV, Direct bilirubin and KICG were the risk factor for PHLF. Functional remKICG was considered the most reliable prediction formula.

Left Hepatectomy with Combined Resection and Reconstruction of Right Hepatic Artery for Bismuth Type I and II Perihilar Cholangiocarcinoma.

Right hepatectomy with caudate lobectomy (RHx) is considered an appropriate procedure for Bismuth type I/II perihilar cholangiocarcinoma in terms of its anatomical and oncological aspect. However, validity of left hepatectomy with caudate lobectomy (LHx) concomitant with arterial resection and reconstruction (AR) is not fully evaluated. The patients who underwent surgical resection for Bismuth type I/II perihilar cholangiocarcinoma between 2002 and 2013 were studied. The standard procedure for Bismuth type I/II cholangiocarcinoma in the institute was RHx, while in patients who had insufficient functional reserve of the left liver, LHx was selected, irrespective of the necessity of AR. The clinicopathologic and perioperative outcomes after LHx + AR were compared with those after RHx. The surgical procedures comprised LHx + AR in 12 and RHx in 24. The left liver volume and left liver functional reserve were significantly lower with LHx + AR than with RHx (left liver volume: 28.0 vs. 33.7%, p = 0.026; estimated indocyanine green clearance of the left liver: 0.036 vs. 0.046, p < 0.001). The rate of surgical morbidity was almost identical between the two procedures. No arterial reconstruction-related complications occurred. The overall 3- and 5-year survival rates and median survival time were 66.7%, 41.7% and 44months for LHx + AR and 70.8%, 49.0% and 57months for RHx (p = 0.640). LHx + AR for Bismuth type I/II perihilar cholangiocarcinoma is considered to be a valid alternative to RHx in patients with an insufficient left liver functional reserve.

Indocyanine green retention test in cirrhosis and portal hypertension: Accuracy and relation to severity of disease.

Patients with cirrhosis and portal hypertension often develop complications relating to hepatic excretory dysfunction. The standard measurement of the hepatic excretion is the constant infusion indocyanine green clearance (ICGCI ) technique. The ICG 15-min retention test (ICG-r15) is faster, more patient friendly, and cheaper. The aims were to compare the ICG-r15 test with the standard method, to assess relations to patient characteristics and survival, and to assess the ICG-r15 level in healthy control subjects. This study included 68 patients with cirrhosis and portal hypertension (Child class A/B/C:17/37/14). All patients underwent a full liver vein catheterization and hemodynamic evaluation with determination of ICG-r15 and ICGCI as the reference in a subset of 38 patients. Sixteen healthy control subjects were included for compiling a reference interval. The ICG-r15 was increased in the cirrhotic patients with increasing values in parallel with liver dysfunction (15/41/58%) in Child class A/B/C compared with 7% in the controls (P<0.001). ICG-r15 correlated highly significantly with the ICGCI (r=-0.96, P<0.0001) and in a multivariate regression analysis with hepatic venous pressure gradient, markers of liver dysfunction and hyperdynamic circulation (P<0.05-0.005). In the control group, normal reference values ranged from 0% to 13%. In addition, ICG-r15 was significantly related to mortality in the patient group (P=0.02). Indocyanine green-r15 reflects portal hypertension, the degree of hepatic failure, and survival and may replace the standard ICGCI . A more elaborated reference interval needs to be compiled, and the prognostic value of ICG-r15 should be validated.

Innovative treatment for hepatocellular carcinoma (HCC).

Indocyanine green (ICG) is not new in the field of liver surgery. Early studies performed in the 1980s and 1990s revealed the value of the ICG clearance test in predicting post-hepatectomy morbidity and mortality. ICG clearance and retention tests are crucial for determining precise liver function before liver surgery and offer several benefits for safe surgery. Whereas ICG is well-known and has long history in medicine, recent progress in infrared light technology over the last decade has highlighted another feature of ICG. For example, ICG fluorescence-guided surgery may change the next generation of liver surgery. In the near future, ICG with near-infrared (NIR) light photodynamic therapy (PDT) is expected to become a new treatment method for hepatocellular carcinoma (HCC). Furthermore, several aspects of the mechanisms of ICG accumulation in HCC cells have been revealed by important basic research studies. New imaging technologies and mechanistic findings keep ICG in the spotlight. In this article, we review three recently described topics of ICG which may contribute to the development of innovative and new treatments method for HCC, fluorescence-guided surgery, mechanism of ICG accumulation in HCC cells, PDT for HCC.

Value of Indocyanine Green Clearance Assessment to Predict Postoperative Liver Dysfunction in Patients Undergoing Liver Resection

Schwarz, Christoph C. MD, PhD; Plass, Immanuel CM; Fitschek, Fabian CM; Mittlböck, Martina PhD; Kampf, Stephanie MD; Asenbaum, Ulrika MD; Starlinger, Patrick MD, PhD; Stremitzer, Stefan MD; Bodingbauer, Martin MD; Kaczirek, Klaus MD, FACS Author Information

Outcomes of hepatopancreatoduodenectomy in patients with biliary disease

Introduction: Hepatopancreatoduodenectomy with extensive hepatic resection (M-HPD) remains a difficult and complex surgery. We sought to evaluate our procedures of M-HPD in patients with biliary diseases. Method: We reviewed data from 52 patients who underwent M-HPD between 2001 to 2017. The postoperative course and overall survival (OS) were investigated.The indocyanine green clearance test value (ICG15 min), and the size of future remnant liver volume (FRLV) were used to determine patient tolerance for undergoing each type of hepatectomy. Portal vein embolization (PE) was performed in cases of right hepatectomy or bilateral trisectionectomy 2 or 3 weeks before HPD. Results: The numbers of patients who underwent right hepatectomy, left hepatectomy, left trisectionectomy, and right trisectionectomy were 36, 12, 2, and 2, respectively. Forty-five patients had bile duct cancer and 6 had gallbladder cancer. One patient was diagnosed with cholangitis based on pathological investigation. Median [range] values for operative time and blood loss were 722 [552–989] min and 1855 [840-6180] ml, respectively. PTPE was performed in 41 (79%) patients. Postoperative complications with Clavien-Dindo (CD) grade IIIa or higher developed in 33 (63%) patients. The mean operative time in patients with CD grade IIIa or higher was significantly longer than that in patients with CD grade II or lower (p = 0.0103). Median survival time, and 3- and 5-year OS for the entire cohort were 33 months, 48%, and 25%, respectively. Conclusions: Candidates for M-HPD should be selected strictly based on future remnant hepatic function. Complicated procedures requiring prolonged operative time should be avoided.

The assessment of functional remnant liver rate for the hepatectomy based on the fusion image of 3DCT and 99mTc-GSA SPECT

Introduction: Preoperative assessment of future remnant liver (FRL) function is critical for major hepatectomy to avoid postoperative liver failure (PLF).Indocyanine green clearance of the FRL (Krem), which is calculated as the ratio of FRL volume to total liver volume by CT, is reliable index for estimating PLF and its threshold is 0.05. However, Krem assumes homogenous uptake throughout the liver.For damaged livers with functional heterogeneity, fusion images combining 99mTc-GSA SPECT and 3D-CT are helpful to estimate the functional reserve of the FRL. Our aim was to determine the utility of functional Krem (F-Krem) by comparing volumetric Krem (V-Krem). Methods: Between July 2015 to December 2017, 45 patients received preoperative dynamic CT and 99mTc-GSA SPECT and underwent major hepatectomy. We constructed fusion image of 3D-CT and 99mTc-GSA SPECT. V-Krem by CT volumetry and F-Krem by fusion image were compared in each patient to estimate which is more reliable. Results: In 88.9% of the patients, F-Krem was bigger than V-Krem (Figure). The ratio of F-Krem/V-Krem (F/V) was 1.116±0.12 (mean±SD). In the patients with portal vein occlusion (PVO) or large tumor (LT) of 500ml or more, F/V ratio was significantly bigger than that of the other patients: 1.181±0.082 (n=8, PVO)vs.1.097±0.118 (n=37, non-PVO), 1.306±0.174 (n=4,LT)vs.1.11±0.097 (n=41, non-LT), (p=0.01, respectively). There were significantly correlation between F-Krem and postoperative-parameters (T-Bil and platelets counts in POD1,3,7). In 5 patients with V-Krem less than 0.05,a patient had F-Krem more than 0.05, resulting in good post-operative course. Conclusion: In almost patients who need major hepatectomy, F-Krem is bigger than V-Krem, because liver function of the diseased side is impaired compared with residual side. F-Krem is a more reliable index than V-Krem.

Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on hepatic function as measured by transient elastography and indocyanine green clearance in patients with short bowel syndrome

Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on hepatic function as measured by transient elastography and indocyanine green clearance in patients with short bowel syndrome

99mTc-GSA SPECT/CT fusion imaging for hepatectomy candidates with extremely deteriorated ICG value.

The value of indocyanine green (ICG) test is negatively affected in patients with intrahepatic shunt, ICG excretory defect, or jaundice. This study evaluated 99mTc-GSA SPECT/CT fusion imaging for assessing liver function in patients with severely deteriorated ICG values. Thirteen hepatectomy candidates with ICG retention rates over 40% were retrospectively analyzed. The ICG clearance rate (KICG) and estimated KICG obtained by 99mTc-GSA scintigraphy (KGSA) were used to evaluate preoperative whole liver function. Remnant liver function was assessed using the remnant (rem) KICG (= KICG × volumetric rate) and remKGSA (= KGSA × functional rate) indices; hepatectomy was considered unsafe for values < 0.05. The correlations of remKICG and remKGSA with postoperative mortality and morbidity were also investigated. KGSA values were significantly greater than KICG values (median: 0.12 vs. 0.059; p < 0.01); remKGSA values were greater than remKICG values in all patients (median: 0.107 vs. 0.0413; p < 0.01). Hepatectomy was considered unsafe in 70% patients using remKICG, and in none of those using remKGSA; liver failure or postoperative mortality did not occur. 99mTc-GSA SPECT/CT fusion imaging enables more accurate liver function assessment than the ICG test in patients with severely deteriorated ICG values.