Galactosyl Human Serum Albumin Research Articles

[68Ga]Ga-NODAGA-TriGalactan, a low molecular weight tracer for the non-invasive imaging of the functional liver reserve

BackgroundDetermination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure.ResultsFor synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA.Conclusion[68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique.

Impact of clinically relevant posthepatectomy liver failure predicted by preoperative evaluation of functional remnant hepatic reserve

Abstract Background: Few studies have investigated the remnant hepatic functional reserve before hepatectomy by calculating the functional remnant liver rate (RLR) using threedimensional computed tomography (3D-CT)/technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) single-photon emission CT (SPECT) fusion imaging. We aimed to preoperatively evaluate the predictive value of functional remnant liver rate (RLR) and indocyanine green (ICG) disappearance rate (KICG) in determining the occurrence of posthepatectomy liver failure (PHLF). Summary of Background Data: The conventional method of volumetric rem-KICG calculated from remnant liver volume and the KICG is difficult to accurately reflect heterogenous remnant liver function. Methods: In total, 106 patients who underwent major hepatectomy were retrospectively analysed. Of these, 24 (22.6%) developed clinically relevant PHLF grades B/C. We examined the ICG retention rate at 15 min (ICGR15) and KICG and constructed a 3DCT/ 99mTc-GSA SPECT fusion image to calculate the volumetric RLR, functional RLR, volumetric rem-KICG, and functional rem-KICG. Results: The multivariate analysis showed functional rem-KICG as the strongest independent risk factor for PHLF grade B/C. The functional-to-volumetric RLR ratios in the patients with portal vein obstruction and/or tumor volume of ≥500 mL was significantly higher. The volumetric rem-KICG determined that hepatectomy was unsafe in 7 patients, whereas the functional rem-KICG determined that it was unsafe in 3 patients. Conclusions: Functional rem-KICG was more reliable than volumetric rem-KICG in predicting clinically relevant PHLF grade B/C, as the resected side’s hepatic status highly influenced the function of the remnant liver. This finding could lead to a wider application of this technique.

Evaluation of Liver Functionality after Liver Stereotactic Body Radiation Therapy (SBRT) Using Blood Tests and Imaging Examinations

Several studies have shown that liver function can be evaluated after hepatic stereotactic body radiation therapy (SBRT) using galactosyl human serum albumin (GSA) liver scintigraphy and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). However, there are no reports investigating the relationship (including Chile-Pugh classification) between imaging and blood tests. Therefore, we investigated the changes that occur in the liver between before and after SBRT by combining imaging (GSA, computed tomography (CT), and MRI) with blood tests that assess total liver function (albumin-bilirubin (ALBI) grade, ICG-R15). We decided to find a method that could assess liver reserve capacity locally and globally MATERIALS/METHODS: Of the 23 patients who underwent hepatic SBRT, 12 patients underwent GSA, MRI, and ICG-R15 testing before treatment, 1 month after treatment, and 3 months after treatment. All patients underwent imaging studies and blood tests at the beginning of treatment, 1 month after treatment, and 3 months after treatment ended. The evaluation items were as follows: 1) changes over time in Child-Pugh classification, ICG-R15, and ALBI values before and after SBRT; 2) changes over time in GSA count and ICG; and 3) selection of the optimal sequence for recognizing radiation hepatitis on MRI. The ICG values were 14.4 before RT, 17.1 after 1 month, and 17.6 after 3 months. ICG worsened after 1 month of treatment, but was similar after 3 months. ALBI values were -2.61 before RT, -2.67 after 1 month, and -2.71 after 3 months. ALBl worsened slightly over time. Regarding the ICG-R15, there was an average worsening of 2.8 after 1 month of treatment compared with before SBRT, but only of 0.5 between 1 month and 3 months after SBRT. Therefore, evaluation using ICG-R15 after SBRT after 1 month alone may be sufficient.

Combining 99mTc-GSA single-photon emission-computed tomography and Gd-EOB-DTPA-enhanced magnetic resonance imaging for staging liver fibrosis.

Preoperative assessment of the degree of liver fibrosis is important to determine treatment strategies. In this study, galactosyl human serum albumin single-photon emission-computed tomography and ethoxybenzyl (EOB) contrast-enhanced magnetic resonance imaging (MRI) were used to assess the changes in hepatocyte function after liver fibrosis, and the standardized uptake value (SUV) was combined with gadolinium EOB-diethylenetriaminepentaacetic acid to evaluate its added value for liver fibrosis staging. A total of 484 patients diagnosed with hepatocellular carcinoma who underwent liver resection between January 2010 and August 2018 were included. Resected liver specimens were classified based on pathological findings into nonfibrotic and fibrotic groups (stratified according to the Ludwig scale). Galactosyl human serum albumin-single-photon emission-computed tomography and EOB contrast-enhanced MRI examinations were performed, and the mean SUVs (SUVmean) and contrast enhancement indices (CEIs) were obtained. The diagnostic value of the acquired SUV and CEIs for fibrosis was assessed by calculating the area under the receiver operating characteristic curve (AUC). In the receiver operating characteristic analysis, SUV + CEI showed the highest AUC in both fibrosis groups. In particular, in the comparison between fibrosis groups, SUV + CEI showed significantly higher AUCs than SUV and CEI alone in discriminating between fibrosis (F3 and 4) and no or mild fibrosis (F0 and 2) (AUC: 0.879, vs SUV [P = 0.008], vs. CEI [P = 0.023]), suggesting that the combination of SUV + CEI has greater diagnostic performance than the individual indices. Combining the SUV and CEI provides high accuracy for grading liver fibrosis, especially in differentiating between grades F0 and 2 and F3-4. SUV and gadolinium EOB-diethylenetriaminepentaacetic acid-enhanced MRI can be noninvasive diagnostic methods to guide the selection of clinical treatment options for patients with liver diseases.

99mTc-GSA scintigraphy for assessing the functional volume ratio of the future liver remnant in the routine practice of liver resection

BackgroundThe significance of incorporating regional functional heterogeneity assessment by liver scintigraphy into the calculation of the future liver remnant has been reported. However, liver scintigraphy entails additional costs and radiation exposure. Nevertheless, studies describing when liver scintigraphy demonstrates an actual benefit over computed tomography liver volumetry are lacking. Thus, we evaluated the degree of agreement between future liver remnant % values calculated by technetium 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy (galactosyl human serum albumin–based future liver remnant %) and those by computed tomography volumetry and investigated the practical impact of performing regional functional heterogeneity assessment. MethodsThe Bland–Altman method was used to retrospectively analyze the agreement between computed tomography– and galactosyl human serum albumin–based future liver remnant % measurements in 84 patients. ResultsIn ordinary patients with a computed tomography–based future liver remnant % greater than 50%, there was a good agreement between both measurements. However, in cases with a computed tomography–based future liver remnant % less than 40%, galactosyl human serum albumin–based measurements were significantly smaller than computed tomography–based values, with 88% of these patients exhibiting a galactosyl human serum albumin–based future liver remnant % less than 30%. After portal vein embolization, galactosyl human serum albumin–based measurements were primarily greater than or in agreement with computed tomography–based values, even in cases with a computed tomography–based future liver remnant % less than 40%. ConclusionAdding 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy to computed tomography liver volumetry is advised when deciding on hepatectomy in patients with a computed tomography–based future liver remnant % less than 50%. If the computed tomography–based future liver remnant % is smaller than 40%, it is strongly recommended to check future liver remnant % by 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy. In other cases, computed tomography–based future liver remnant % calculation alone can be regarded as the gold standard of safe hepatectomy.

Targeted delivery of maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial.

A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed. Host-guest interaction between a galactosyl dye and human serum albumin (HSA) produces supramolecular galactoside-HSA conjugates, which are then used to coat 2D MoS2. The 2D glycomaterial was shown to be capable of the targeted delivery of maytansine to a liver cancer cell line that highly expresses a galactose receptor, resulting in greater cytotoxicity than maytansine alone.

Tc-99m GSA scintigraphy within the first 3\xa0days after admission as an early predictor of outcome in severe acute liver injury

Patients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P < 0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832–0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.

Coil volume embolization ratio for preventing recanalization after portal vein embolization.

The purpose of this study was to evaluate the optimum volume embolization ratio (VER) for the prevention of recanalization after portal vein embolization (PVE) and the influence of recanalization on future liver remnant (FLR) function using technetium-99m galactosyl human serum albumin single-photon emission computed tomography (99mTc-GSA SPECT/CT) fusion imaging. We analyzed procedural data of 18 patients who underwent PVE from 2015 to 2018. A total of 29 portal branches were embolized (12 anterior branch, 11 posterior branch, 4 left branch, 2 right branch) with absolute ethanol and coils. Portal vein recanalization was evaluated three weeks after PVE by contrast-enhanced CT. We classified the treated portal branches as non-recanalized and recanalized. VER was compared between the groups. In addition, for each patient, we calculated and evaluated the ratio of FLR volume to total liver volume (volumetric %FLR), FLR count to total liver count on 99mTc-GSA SPECT/CT fusion imaging (functional %FLR), and functional-volumetric ratio (functional %FLR/ volumetric %FLR). Twenty-six portal branches showed no recanalization (non-recanalized group, n=26, 89.7%), while three portal branches showed recanalization (recanalized group, n=3, 10.3%). The median VER was 4.94% (3.12%-11.1%) in the non-recanalized group and 3.49% (2.76%-4.32%) in the recanalized group, which was significantly different between the groups (p = 0.045, Mann-Whitney U test). The median functional-volumetric ratio was 1.16 (1.03-1.50) in non-recanalized patients (n=15, 83.3%) and 1.01 (0.96-1.13) in recanalized patients (n=3, 16.7%), and it was significantly higher in the non-recanalized patients (p = 0.021, Mann-Whitney U test). The VER for preventing recanalization after PVE was approximately 5% (> 4.94%). 99mTc-GSA SPECT/CT fusion imaging revealed a decrease in FLR function due to recanalization after PVE.

Sustained hyperbilirubinemia following clarithromycin administration

Abstract Rationale: Hyperbilirubinemia is observed in drug-induced liver injury of cholestatic type, but direct inhibition of transporter proteins which facilitates bilirubin transport also causes hyperbilirubinemia. Here we present a case of sustained hyperbilirubinemia after the administration of clarithromycin. Patient concerns: A 52-year-old man was referred to our hospital because of sustained hyperbilirubinemia. Both contrast-enhanced computed tomography and Magnetic resonance cholangiopancreatography did not reveal any abnormality. But his liver was not enhanced in the hepatocellular phase of Gd-EOB-DTPA MRI. Indocyanine Green (ICG) retention rate at 15 minutes (ICG(R15)) was 58%, urinary coproporphyrin was 324 μg/g Cr, and serum bile acid was 283 nmol/mL. Technetium-99m galactosyl human serum albumin (99mTc-GSA) liver scintigram revealed that his liver function was normal (blood clearance ratio (HH15), 0.572; and hepatic uptake ratio (LHL15), 0.948) Diagnoses: These findings suggested that hyperbilirubinemia in the present case was caused by impaired organic anion-transporting polypeptide (OATP) 1B1 and 1B3 activity. Drug-induced lymphocyte stimulation test (DLST) for clarithromycin was positive. Among the drugs prescribed before the presentation of hyperbilirubinemia, clarithromycin is the only agent that has been reported to reduce the OATP1B1/1B3 transporter activity. Interventions: The patient continued taking oral UDCA, but hyperbilirubinemia did not improve. Bilirubin absorption therapy was performed twice. Outcomes: Following bilirubin absorption therapy, hyperbilirubinemia resolved and the bilirubin levels became normal. With the decrease in serum bilirubin, the liver was normally enhanced on the hepatocellular phase of Gd-EOB-DTPA MRI. ICG(R15). Urinary coproporphyrin, and bile acid levels returned to normal range (ICG(R15) of 9.2%, urinary coproporphyrin of 58 μg/g Cr, and bile acid of 13.5 nmol/mL). Lessons: The present case indicates that uptake of Gd-EOB-DTPA in the liver, ICG retention test, serum bile acid levels combined with urinary coproporphyrin can be a potential marker of OATP transporter activity and help in differential diagnosis of sustained hyperbilirubinemia.

The value of 99mTc-labeled galactosyl human serum albumin single-photon emission computerized tomography/computed tomography on regional liver function assessment and posthepatectomy failure prediction in patients with hilar cholangiocarcinoma.

The aim was to evaluate the value of Tc-labeled galactosyl human serum albumin (Tc-GSA) with single-photon emission computerized tomography (SPECT) in the preoperative assessment of regional liver function and prediction of posthepatectomy liver failure (PHLF) in patients with hilar cholangiocarcinoma (hCCA). Patients with hCCA who underwent Tc-GSA SPECT/computed tomography (CT) before hepatectomy were included. The liver functional parameters of functional liver density (FLD) and predictive residual index (PRI) were calculated based on Tc-GSA SPECT/CT. PHLF was defined according to the International Study Group of Liver Surgery criteria. Univariate and multivariate analyses were used to analyze the risk factors for PHLF. The prediction of PHLF was calculated using receiver operating characteristic curve. A total of 34 patients were included, 23 of whom underwent preoperative biliary drainage. FLD was significantly higher in patients with drained lobes than that in patients with undrained lobes (0.615 ± 0.190 versus 0.500 ± 0.211, P < 0.05). Sixteen patients suffered PHLF. The ratio of future remnant to total morphological liver volume, future remnant FLD, and PRI differed significantly in patients with and without PHLF according to univariate analysis. PRI was identified as the only independent factor for prediction of PHLF according to multivariate analysis. With a PRI of 0.78, it was possible to predict PHLF with a sensitivity of 83% and a specificity of 93%. Tc-GSA SPECT/CT can accurately assess regional liver function and is better able to predict PHLF than conventional methods in patients with hCCA.

Validation set analysis to predict postoperative outcomes by technetium-99m galactosyl serum albumin scintigraphy for hepatectomy.

The indocyanine green retention rate at 15 min (ICGR15) is a gold standard parameter of liver function when deciding on the extent of hepatectomy. However, ICGR15 is influenced by several hepatic conditions. To evaluate auxiliary preoperative liver functional reserve, we examined the clinical significance of modified parameters by blood tests and technetium-99m galactosyl human serum albumin (Tc-GSA) scintigraphy. We measured liver function parameters, including the hepatic uptake ratio (LHL15) and the blood pool clearance index (HH15) of Tc-GSA and their modified formulae [LHL/HH15, LHL minus HH15, and converted ICGR15 (cICGR15) from a preliminary study] in 229 patients, including 18 with biliary obstruction. The mean values of LHL15/HH15, LHL minus HH15, and cICGR15 were 1.646 ± 0.295, 0.347 ± 0.116, and 13.2 ± 5.3%, respectively. These parameters correlated significantly with other liver functions measured by blood tests except for the bilirubin level (P < 0.05) although the actual ICGR15 level correlated positively with the bilirubin level. The difference of ICGR15 (ICGR15 minus cICGR15) in patients with biliary obstruction tended to be higher in comparison with that in patients without biliary obstruction (P = 0.044). Values of LHL/HH15, LHL minus HH15, and the cICGR15 were not significantly associated with postoperative complications. The modified parameters of Tc-GSA were useful for evaluating hepatic function in patients with high bilirubinemia due to biliary obstruction. However, it remains difficult to establish a more reliable parameter as a standard hepatic function test instead of ICGR15.

Correlation between Liver Elasticity by Ultrasound Elastography and Liver Functional Reserve

No worldwide consensus on the assessment tool for liver functional reserve is currently available. The aim of this study was to evaluate the correlation between liver elasticity of both hepatic lobes and liver functional reserve tests. This prospective observational study comprised 40 patients scheduled for hepatectomy. Liver elasticity was assessed by Virtual Touch Quantification (VTQ). The mean VTQ value for the right and left lobes was defined as the mVTQ. Liver functional reserve was measured with technetium-99m-diethylenetriaminepentaacetic acid–galactosyl-human serum albumin scintigraphy as LHL15 and HH15 and the indocyanine green (ICG) excretion test as ICG-R15 and ICG-K. All examinations were measured after biliary decompression confirmed serum a total bilirubin level ≤2 mg/dL. Mean VTQ values were moderately correlated with LHL15 (r = −0.42, p < 0.01), HH15 (r = 0.48, p < 0.01), ICG-R15 (r = 0.53, p < 0.01) and ICG-K (r = −0.61, p < 0.01) values. In conclusion, the liver elasticity determined by VTQ would be a useful predictor of liver functional reserve in patients scheduled for hepatectomy.

Validation of Functional Assessment for Liver Resection Considering Venous Occlusive Area after Extended Hepatectomy

BackgroundPrevious studies demonstrated that liver function in a veno-occlusive region is approximately 40% of that in a non-veno-occlusive region after hepatectomy with excision of major hepatic vein. We validated the preoperative assessment of future remnant liver (FRL) function based on 40% decreased function of the veno-occlusive region. MethodsSixty patients who underwent hepatectomy with excision of major hepatic vein were analyzed. The FRL functions of the veno-occlusive and non-veno-occlusive regions were calculated with 99mTc–galactosyl human serum albumin scintigraphy single-proton emission computed tomography fusion system and SYNAPSE VINCENT® preoperatively. Risk assessment for hepatectomy was evaluated based on indocyanine green retention at 15 min, and patients with insufficient FRL function were described as marginal. ResultsThe median volume and function of the veno-occlusive region per whole liver were 111 ml and 11.0%, respectively. When the function of the veno-occlusive region was presumed as 0%, 40%, and 100%, the FRL function was 62.5%, 68.4%, and 75.0% and 21, 15, and 7 patients were classified as marginal, respectively. When the function of the veno-occlusive region was presumed as 40%, the posthepatectomy liver failure (PHLF) rate of marginal patients was significantly higher than that of safe patients (46.7% vs 8.9%, P = 0.002). Multivariable analysis indicated that marginal FRL function based on 40% decreased function of the veno-occlusive region was the only independent risk factor for PHLF (odds ratio 8.97, P = 0.002) after extended hepatectomy. ConclusionAssessment of preoperative FRL function based on 40% decreased function of the veno-occlusive region may have high validity.

Using 99mTc-DTPA galactosyl human serum albumin liver scintigraphy as a prognostic indicator in jaundice-free patients with biliary atresia

BackgroundWe evaluated the clinical significance of follow-up data, including 99mTc-DTPA galactosyl human serum albumin (99mTc-GSA) liver scintigraphy data, as prognostic indicators for jaundice-free patients with biliary atresia (BA). MethodsOf 87 patients who underwent Kasai portoenterostomy (KP) between 1991 and 2012, 45 jaundice-free patients aged 1–2 years underwent 99mTc-GSA scintigraphy and were classified into 2 groups: those who survived with a native liver (Group A, n = 34) and those who required liver transplantation (LTx) (Group B, n = 11). We compared 99mTc-GSA scintigraphy data (HH15, LHL15, and HH15/LHL15 [H/L15]) and liver function test (LFT) results between the groups. The patients underwent a second 99mTc-GSA scintigraphy at approximately 5 years of age. ResultsAll patients survived. HH15, H/L15, total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, and alanine transaminase levels were higher in Group B than in Group A (p<0.05). Total and direct bilirubin levels were associated with H/L15 (p<0.05). There were no significant changes in results between the first and second 99mTc-GSA scintigraphy in Group A. ConclusionsMid- and long-term prognoses may be predicted using 99mTc-GSA scintigraphy data and LFTs in patients aged 1–2 years. We recommend regular monitoring of postoperative data following KP, even in jaundice-free patients. Level of evidenceIII.

Preoperative Chemotherapy on Functional Liver Regeneration for Colorectal Liver Metastases Assessed With 99mTc-GSA SPECT/CT Imaging

Objective:To investigate the functional liver regeneration after chemotherapy and liver resection for colorectal liver metastases (CRLM).Background/Purpose:Preoperative chemotherapy followed by liver resection for CRLM has been increasing; however, its negative impact on liver regeneration remains unknown.Methods:From January 2009 to December 2013, we enrolled 40 selected patients who underwent major hepatectomy without viral hepatitis and severe liver fibrosis. CRLM patients with preoperative chemotherapy (CT-CRLM group, n = 12) and patients without preoperative chemotherapy (control group, n = 28) were evaluated. Liver volume (LV) and functional liver volume (FLV) was assessed using Tc-99m–labeled galactosyl human serum albumin (99mTc-GSA) scintigraphy, single-photon emission computed tomography (SPECT), CT-fused images. Preoperative, future remnant liver, and post 1-month values were compared.Results:Median course of preoperative chemotherapy was 8 (range: 6–16). Preoperative background factors were almost identical including resection rate and functional resection rate. In the CT-CRLM group and in the control group, the percentage increases in LV were 39.3% ± 29.0% and 23.2% ± 23.5% (P = 0.037), and FLV were 79.4% ± 43.1% and 57.0% ± 33.4% (P = 0.417), respectively; absolute differences in LV were 216.2 ± 155.7 cm3 and 148.7 ± 134.7 cm3 (P = 0.086) and FLV were 19.4% ± 8.5%/m2 and 17.4% ± 7.9%/m2 (P = 0.235), respectively. We found no obvious tendency for negative influence on liver functional regeneration by the preoperative regimens for CRLM.Conclusions:Several courses of preoperative chemotherapy may not affect functional liver regeneration for CRLM patients after major hepatectomy.

Application value of dynamic SPECT 99Tcm-GSA scintigraphy assessing regional liver function changes before and after portal vein embolization

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE). Methods The retrospective cross-sectional study was conducted. The clinical data of 11 patients with Bismuth Ⅲa hilar cholangiocarcinoma who were admitted to the General Hospital of People′s Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected. B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma. Dynamic SPECT 99Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV), morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE. Observation indicators: (1) the changes of serum indexes in 2 weeks before and after PVE; (2) the changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE; (3) surgical and postoperative situations of hilar cholangiocarcinoma; (4) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level, with or without peritoneal effusion and survival up to June 2017. Measurement data with normal distribution were represented as ±s. The comparisons of pre-and post-operative data were analyzed by the paired t test. Results (1) The changes of serum indexes in 2 weeks before and after PVE: 11 patients underwent successful right PVE. The alanine aminotransferase (ALT), TBil, albumin (Alb), Platelets (PLT) and prothrombin time (PT) were respectively (113±20)U/L, (73±8)μmol/L, (35.0±2.5)g/L, (209±58)×109/L, (11.4±0.7)seconds in 2 weeks before PVE and (120±18)U/L, (36±7)μmol/L, (34.4±3.2)g/L, (224±82)×109/L, (11.2±0.8)seconds in 2 weeks after PVE, with a statistically significant difference in TBil level (t=-10.592, P 0.05). (2) The changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE: the FLV, MLV and FLD of the whole liver were respectively (894±255)mL, (1 552±504)mL, 0.59±0.14 in 2 weeks before PVE and (812±206)mL, (1 521±422)mL, 0.55±0.16 in 2 weeks after PVE, with no statistically significant difference (t=1.569, 0.666, 1.980, P>0.05). The FLV, MLV and FLD of the embolized lobe were respectively (623±275)mL, (1 047±394)mL, 0.62±0.14 in 2 weeks before PVE and (375±240)mL, (865±337)mL, 0.44±0.24 in 2 weeks after PVE, with statistically significant differences (t=5.909, 3.736, 3.359, P<0.05); the descending percentages were respectively 38.1%, 9.8% and 24.6%. The FLV, MLV and FLD of the non-embolized lobe were respectively (274±152)mL, (530±176)mL, 0.52±0.21 in 2 weeks before PVE and (436±149)mL, (656±133)mL, 0.68±0.24 in 2 weeks after PVE, with statistically significant differences (t=-6.019, -6.345, -3.933, P<0.05); the elevated percentages were respectively 80.1%, 19.9% and 23.8%. (3) Surgical and postoperative situations of hilar cholangiocarcinoma: of 11 patients, 10 received successful peri-hilar right hemihepatectomy, the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively; 1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor. The operation time, volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585±194)minutes, (472±274)mL and (8±5)days. Of 10 patients undergoing operations, 2 were complicated with massive peritoneal effusion at 2 days postoperatively, volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage, and were improved by 1- month conservative treatment; other 8 patients were not complicated with hepatic dysfunction. Duration of hospital stay of 11 patients was (16±4)days. (4) Follow-up and survival situations: 10 patients were followed up for 4-72 months, with a median time of 39 months. During the follow-up, there was no evaluated TBil level and peritoneal effusion in 10 patients. The median survival time, 1-, 3- and 5-year overall survival rates were 88.8%, 74.6% and 36.8%, respectively. Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE. The increased rate of FLV of non-embolized lobe is higher than that of MLV. Key words: Hilar cholangiocarcinoma; Radical resection; Portal vein embolization; Scintigraphy single-photon emission computed tomography; 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection; Regional liver function

Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). Methods: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 − (resected liver weight − tumor volume)/whole liver volume without tumor]. Results: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. Conclusions: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should be carefully monitored for PHLF.

Liver Functional Volumetry by Tc-99m Mebrofenin Hepatobiliary Scintigraphy before Major Liver Resection: A Game Changer.

Future remnant liver function (FRL-F) estimation is important before major liver resection to avoid posthepatectomy liver failure (PHLF). Conventionally, it is estimated by global dynamic liver function tests which assume homogeneous liver function and unable to calculate regional function. Computed tomography is another method to estimate FRL volume but assumes that volume is equivalent to function. Hence, a global and regional non-invasive liver function test is desirable. Studies were identified by MEDLINE, PubMed, and Google Scholar for articles from January 1990 to December 2017 using the following keywords “Mebrofenin, hepatobiliary scintigraphy (HBS), FRL-F, PHLF, portal vein embolization (PVE).” HBS with technetium-99 m galactosyl human serum albumin (Tc-99m GSA) and Tc-99m Mebrofenin is a known test for functional liver assessment. Restricted availability of Tc-99m GSA only in Japan is a main drawback for its global acceptance. However, Tc-99m Mebrofenin is routinely available to the rest of the world. A unique protocol for FRL-F estimation by Tc-99m Mebrofenin is described in detail in this review. Tc-99m Mebrofenin HBS has shown a strong correlation to 15 min indocyanine green clearance. HBS has been reported better in predicting the risk of PHLF with a 2.69%/min/m2 cutoff of FRL-F. Tc-99m Mebrofenin HBS has been found better in stratification of PVE before major liver surgery as well. We concluded, Tc-99m Mebrofenin HBS was unique in calculating global and regional liver function and takes nonuniformity and underlying pathology in the account. Moreover, a single cutoff might fit in all for PHLF risk assessment and PVE stratification.

Usefulness of 99mTc-DTPA galactosyl human serum albumin liver scintigraphy for evaluating hepatic functional reserve after Kasai procedure

Background/purposeWe investigated whether 99mTc-DTPA galactosyl human serum albumin (GSA) liver scintigraphy could help evaluate post-Kasai procedure hepatic functional reserve in order to inform therapeutic strategies, including liver transplantation. MethodsGSA scintigraphy was performed post-Kasai procedure. Patients were classified as having favorable (native liver survival) or poor (liver transplantation or death) prognoses. The clearance index (HH15), receptor index (LHL15), and time at which cumulative liver radioactivity reached 85% of heart plus liver activity (T0.85) were compared to laboratory data and prognosis. ResultsGSA scintigraphy was performed 106 times on 35 patients. T0.85 correlated well with laboratory variables associated with liver function (platelet count, international normalized ratio of prothrombin time, serum albumin, total cholesterol, and cholinesterase). HH15 correlated moderately and LHL15, poorly. HH15 and T0.85 values were significantly higher in the poor-prognosis than in the favorable-prognosis group, and LHL15 was significantly lower. The T0.85 cutoff value (6.25min) corresponded with division into prognosis groups, and had high sensitivity (0.78) and specificity (0.83). ConclusionsHepatic functional reserve post-Kasai procedure can be evaluated using the GSA scintigraphy T0.85 value. A value consistently >6.25min indicates the need for liver transplantation. Type of studyDiagnostic Test. Level of evidenceLevel III.

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30%, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P>.001 and P>.001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P=.357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P=.005; OR 36.5; 95% CI 3.0-446.3) and steatohepatitis (P=.012; OR, 29.1; 95% CI 2.1-400.1). FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.