Non-tumorous Liver Parenchyma Research Articles

Deep Learning-Based Automatic Segmentation Combined with Radiomics to Predict Post-TACE Liver Failure in HCC Patients.

To develop and validate a deep learning-based automatic segmentation model and combine with radiomics to predict post-TACE liver failure (PTLF) in hepatocellular carcinoma (HCC) patients. This was a retrospective study enrolled 210 TACE-trated HCC patients. Automatic segmentation model based on nnU-Net neural network was developed to segment medical images and assessed by the Dice similarity coefficient (DSC). The screened clinical and radiomics variables were separately used to developed clinical and radiomics predictive model, and were combined through multivariate logistic regression analysis to develop a combined predictive model. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were applied to compare the performance of the three predictive models. The automatic segmentation model showed satisfactory segmentation performance with an average DSC of 83.05% for tumor segmentation and 92.72% for non-tumoral liver parenchyma segmentation. The international normalized ratio (INR) and albumin (ALB) was identified as clinically independent predictors for PTLF and used to develop clinical predictive model. Ten most valuable radiomics features, including 8 from non-tumoral liver parenchyma and 2 from tumor, were selected to develop radiomics predictive model and to calculate Radscore. The combined predictive model achieved the best and significantly improved predictive performance (AUC: 0.878) compared to the clinical predictive model (AUC: 0.785) and the radiomics predictive model (AUC: 0.815). This reliable combined predictive model can accurately predict PTLF in HCC patients, which can be a valuable reference for doctors in making suitable treatment plan.

MRI features for predicting the pathological grade of HCC in patients undergoing liver transplantation

BackgroundContrast-enhanced magnetic resonance imaging (MRI) plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC). This study aims to assess the performance of MRI features for evaluating hepatocellular carcinoma (HCC) aggressiveness in living liver transplantation in patients.Material and methodsThis retrospective study included patients who underwent liver transplantation in our hospital between 2015 and 2020. Abdominal contrast-enhanced MRIs of these patients were reviewed, and clinical, radiological, and histopathological findings of HCCs were recorded. The prognostic features of HCCs as determined by MRI were compared with Edmondson-Steiner (E-S) grades. Liver parenchyma fibrosis based on an apparent diffusion coefficient (ADC) map was correlated with histological subclassification of cirrhosis using the Laennec staging system.ResultsThe study subjects included 37 men and 8 women with a mean age of 59.56 ± 7.81 (range: 25–72). The mean tumour size was 37.33 ± 22.27 mm (range: 10–118 mm), and nine tumours (23.1%) involved portal vein tumour thrombosis. There was a significant correlation between tumour grade and size (p = 0.007) and intratumoral fat (p = 0.014) even though no significant correlations between grade and mean ADC value, capsule appearance, presence of satellite lesions, smooth margin, imaging of the tumour feeding artery, and corona enhancement of HCC (p > 0.05) were found. There was a statistically significant correlation between mild (stage 4A) and moderate (stage 4B) fibrosis of non-tumorous liver parenchyma and ADC value (p < 0.001).ConclusionOur study found that ADC values can be used to distinguish mild cirrhotic livers from moderate cirrhotic livers. Diffusion MRI might be used to diagnose the degree of liver fibrosis without histopathological analysis. According to our results, only intralesional fat and tumour size correlated with tumour grade, and as such, these parameters could be used as prognostic MRI biomarkers for HCC.

A virtual biopsy of liver parenchyma to predict the outcome of liver resection.

The preoperative risk assessment of liver resections (LR) is still an open issue. Liver parenchyma characteristics influence the outcome but cannot be adequately evaluated in the preoperative setting. The present study aims to elucidate the contribution of the radiomic analysis of non-tumoral parenchyma to the prediction of complications after elective LR. All consecutive patients undergoing LR between 2017 and 2021 having a preoperative computed tomography (CT) were included. Patients with associated biliary/colorectal resection were excluded. Radiomic features were extracted from a virtual biopsy of non-tumoral liver parenchyma (a 2mL cylinder) outlined in the portal phase of preoperative CT. Data were internally validated. Overall, 378 patients were analyzed (245 males/133 females-median age 67years-39 cirrhotics). Radiomics increased the performances of the preoperative clinical models for both liver dysfunction (at internal validaton, AUC = 0.727 vs. 0.678) and bile leak (AUC = 0.744 vs. 0.614). The final predictive model combined clinical and radiomic variables: for bile leak, segment 1 resection, exposure of Glissonean pedicles, HU-related indices, NGLDM_Contrast, GLRLM indices, and GLZLM_ZLNU; for liver dysfunction, cirrhosis, liver function tests, major hepatectomy, segment 1 resection, and NGLDM_Contrast. The combined clinical-radiomic model for bile leak based on preoperative data performed even better than the model including the intraoperative data (AUC = 0.629). The textural features extracted from a virtual biopsy of non-tumoral liver parenchyma improved the prediction of postoperative liver dysfunction and bile leak, implementing information given by standard clinical data. Radiomics should become part of the preoperative assessment of candidates to LR.

Contrast-Enhanced Imaging Features and Clinicopathological Investigation of Steatohepatitic Hepatocellular Carcinoma

Steatohepatitic hepatocellular carcinoma (SH-HCC) is a distinctive histologic variant of HCC for the presence of steatohepatitis. This study intended to evaluate the contrast-enhanced imaging features and clinicopathological characteristics of 26 SH-HCCs in comparison with 26 age-and-sex-matched non-SH-HCCs. The frequency of obesity (34.6%, p = 0.048) and type 2 diabetes mellitus (23.1%, p = 0.042) were significantly higher in SH-HCC patients. As seen via B-mode ultrasound (BMUS), SH-HCCs were predominantly hyperechoic (65.4%, p = 0.002) lesions, while non-SH-HCCs were mainly hypo-echoic. As seen via contrast-enhanced ultrasound (CEUS), 96.2% of SH-HCCs exhibited hyperenhancement in the arterial phase. During the portal venous and late phase, 88.5% of SH-HCCs showed late and mild washout. Consequently, most SH-HCCs and all non-SH-HCCs were categorized as LR-4 or LR-5. As seen via magnetic resonance imaging (MRI), a signal drop in the T1WI opposed-phase was observed in 84.6% of SH-HCCs (p = 0.000). Notably, diffuse fat in mass was detected in 57.7% (15/26) SH-HCCs (p < 0.001). As seen via contrast-enhanced MRI (CEMRI), most of the SH-HCCs and non-SH-HCCs exhibited heterogeneous hyperenhancement in the arterial phase (80.8% versus 69.2%, p = 0.337). During the delayed phase, 76.9% SH-HCCs and 88.5% non-SH-HCCs exhibited hypo-enhancement. Histopathologically, the rate of microvascular invasion (MVI) was significantly lower in SH-HCCs than non-SH-HCCs (42.3% versus 73.1%, p = 0.025). The frequency of hepatic steatosis >5% in non-tumoral liver parenchyma of SH-HCCs was significantly higher than in non-SH-HCCs (88.5% versus 26.9%, p = 0.000). Additionally, the fibrotic stages of S0, S1 and S2 in SH-HCCs were significantly higher than in non-SH-HCCs (p = 0.044). During follow-up, although the PFS of SH-HCC patients was significantly longer than non-SH-HCC patients (p = 0.046), for the overall survival rate of SH-HCC and non-SH-HCC patients there was no significant difference (p = 0.162). In conclusion, the frequency of metabolism-related diseases in SH-HCC patients was significantly higher than in non-SH-HCC patients. The imaging features of SH-HCCs combined the fatty change and typical enhancement performance of standard HCC as seen via CEUS/CEMRI.

Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis.

Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.

Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was measured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test. Results The study included 119 patients (mean age, 60 years ± 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in responders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treatments, with better discrimination than RECIST and mRECIST. Keywords: CT, Chemoembolization, Embolization, Abdomen/GI, Liver Supplemental material is available for this article. © RSNA, 2023.

Radioembolization-Induced Changes in Hepatic [18F]FDG Metabolism in Non-Tumorous Liver Parenchyma.

Background: [18F]FDG-PET/CT is increasingly used for response assessments after oncologic treatment. The known response criteria for [18F]FDG-PET/CT use healthy liver parenchyma as the reference standard. However, the [18F]FDG liver metabolism results may change as a result of the given therapy. The aim of this study was to assess changes in [18F]FDG liver metabolism after hepatic 90Y resin radioembolization. Methods: [18F]FDG-PET/CT scans prior to radioembolization and one and three months after radioembolization (consistent with the PERCIST comparability criteria), as well as 90Y-PET/CT scans, were analyzed using 3 cm VOIs. The FDG activity concentration and absorbed dose were measured. A linear mixed-effects logistic regression model and logistic mixed-effects model were used to assess the correlation between the FDG-activity concentration, absorbed dose, and biochemical changes. Results: The median SULVOI,liver at baseline was 1.8 (range = 1.2–2.8). The mean change in SULVOI,liver per month with an increase in time was 0.05 (95%CI 0.02–0.09) at p < 0.001. The median absorbed dose per VOI was 31.3 Gy (range = 0.1–82.3 Gy). The mean percent change in ΔSULVOI,liver for every Gy increase in the absorbed dose was –0.04 (95%CI −0.22–0.14) at p = 0.67. The SULblood and SULspleen results showed no increase. Conclusions: The [18F]FDG metabolism in the normal liver parenchyma is significantly but mildly increased after radioembolization, which can interfere with its use as a threshold for therapy response.

Contrast Administration Impacts CT-Based Radiomics of Colorectal Liver Metastases and Non-Tumoral Liver Parenchyma Revealing the "Radiological" Tumour Microenvironment.

The impact of the contrast medium on the radiomic textural features (TF) extracted from the CT scan is unclear. We investigated the modification of TFs of colorectal liver metastases (CLM), peritumoral tissue, and liver parenchyma. One hundred and sixty-two patients with 409 CLMs undergoing resection (2017–2020) into a single institution were considered. We analyzed the following volumes of interest (VOIs): The CLM (Tumor-VOI); a 5-mm parenchyma rim around the CLM (Margin-VOI); and a 2-mL sample of parenchyma distant from CLM (Liver-VOI). Forty-five TFs were extracted from each VOI (LIFEx®®). Contrast enhancement affected most TFs of the Tumor-VOI (71%) and Margin-VOI (62%), and part of those of the Liver-VOI (44%, p = 0.010). After contrast administration, entropy increased and energy decreased in the Tumor-VOI (0.93 ± 0.10 vs. 0.85 ± 0.14 in pre-contrast; 0.14 ± 0.03 vs. 0.18 ± 0.04, p < 0.001) and Margin-VOI (0.89 ± 0.11 vs. 0.85 ± 0.12; 0.16 ± 0.04 vs. 0.18 ± 0.04, p < 0.001), while remaining stable in the Liver-VOI. Comparing the VOIs, pre-contrast Tumor and Margin-VOI had similar entropy and energy (0.85/0.18 for both), while Liver-VOI had lower values (0.76/0.21, p < 0.001). In the portal phase, a gradient was observed (entropy: Tumor > Margin > Liver; energy: Tumor < Margin < Liver, p < 0.001). Contrast enhancement affected TFs of CLM, while it did not modify entropy and energy of parenchyma. TFs of the peritumoral tissue had modifications similar to the Tumor-VOI despite its radiological aspect being equal to non-tumoral parenchyma.

Virtual Biopsy for Diagnosis of Chemotherapy-Associated Liver Injuries and Steatohepatitis: A Combined Radiomic and Clinical Model in Patients with Colorectal Liver Metastases.

Simple SummaryPatients receiving chemotherapy for liver metastases from colorectal cancer may develop liver injuries that impair hepatic function and postoperative outcome. The non-invasive diagnosis of these damages is still an unmet need. Recently, advanced imaging analysis techniques, including the so-called “radiomics”, achieved adequate prediction of pathology data. The present study demonstrated that radiomic analysis of liver parenchyma in combination with clinical and laboratory data improves non-invasive diagnosis of chemotherapy-related liver injuries. Non-invasive diagnosis of chemotherapy-associated liver injuries (CALI) is still an unmet need. The present study aims to elucidate the contribution of radiomics to the diagnosis of sinusoidal dilatation (SinDil), nodular regenerative hyperplasia (NRH), and non-alcoholic steatohepatitis (NASH). Patients undergoing hepatectomy for colorectal metastases after chemotherapy (January 2018-February 2020) were retrospectively analyzed. Radiomic features were extracted from a standardized volume of non-tumoral liver parenchyma outlined in the portal phase of preoperative post-chemotherapy computed tomography. Seventy-eight patients were analyzed: 25 had grade 2–3 SinDil, 27 NRH, and 14 NASH. Three radiomic fingerprints independently predicted SinDil: GLRLM_f3 (OR = 12.25), NGLDM_f1 (OR = 7.77), and GLZLM_f2 (OR = 0.53). Combining clinical, laboratory, and radiomic data, the predictive model had accuracy = 82%, sensitivity = 64%, and specificity = 91% (AUC = 0.87 vs. AUC = 0.77 of the model without radiomics). Three radiomic parameters predicted NRH: conventional_HUQ2 (OR = 0.76), GLZLM_f2 (OR = 0.05), and GLZLM_f3 (OR = 7.97). The combined clinical/laboratory/radiomic model had accuracy = 85%, sensitivity = 81%, and specificity = 86% (AUC = 0.91 vs. AUC = 0.85 without radiomics). NASH was predicted by conventional_HUQ2 (OR = 0.79) with accuracy = 91%, sensitivity = 86%, and specificity = 92% (AUC = 0.93 vs. AUC = 0.83 without radiomics). In the validation set, accuracy was 72%, 71%, and 91% for SinDil, NRH, and NASH. Radiomic analysis of liver parenchyma may provide a signature that, in combination with clinical and laboratory data, improves the diagnosis of CALI.

An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma. The results showed that colorectal primary constituted the largest proportion of metastatic carcinoma showing β-catenin overexpression. Intra-tumoral CD8 count was lower and FoxP3 count was higher when compared with the non-tumoral liver parenchyma. β-catenin overexpression was associated with a lower CD8 count in the tumor region (p = 0.003). In summary, our findings are in support of an altered immune tumor microenvironment vs. the non-tumor liver tissues in the metastatic site. Suppression of CD8 count was associated with activated Wnt/β-catenin signaling in the metastatic tumor.

Quantitative comparison of pre-treatment predictive and post-treatment measured dosimetry for selective internal radiation therapy using cone-beam CT for tumor and liver perfusion territory definition

BackgroundSelective internal radiation therapy (SIRT) is a promising treatment for unresectable hepatic malignancies. Predictive dose calculation based on a simulation using 99mTc-labeled macro-aggregated albumin (99mTc-MAA) before the treatment is considered as a potential tool for patient-specific treatment planning. Post-treatment dose measurement is mainly performed to confirm the planned absorbed dose to the tumor and non-tumor liver volumes. This study compared the predicted and measured absorbed dose distributions.MethodsThirty-one patients (67 tumors) treated by SIRT with resin microspheres were analyzed. Predicted and delivered absorbed dose was calculated using 99mTc-MAA-SPECT and 90Y-TOF-PET imaging. The voxel-level dose distribution was derived using the local deposition model. Liver perfusion territories and tumors have been delineated on contrast-enhanced CBCT images, which have been acquired during the 99mTc-MAA work-up. Several dose-volume histogram (DVH) parameters together with the mean dose for liver perfusion territories and non-tumoral and tumoral compartments were evaluated.ResultsA strong correlation between the predicted and measured mean dose for non-tumoral volume was observed (r = 0.937). The ratio of measured and predicted mean dose to this volume has a first, second, and third interquartile range of 0.83, 1.05, and 1.25. The difference between the measured and predicted mean dose did not exceed 11 Gy. The correlation between predicted and measured mean dose to the tumor was moderate (r = 0.623) with a mean difference of − 9.3 Gy. The ratio of measured and predicted tumor mean dose had a median of 1.01 with the first and third interquartile ranges of 0.58 and 1.59, respectively. Our results suggest that 99mTc-MAA-based dosimetry could predict under or over dosing of the non-tumoral liver parenchyma for almost all cases. For more than two thirds of the tumors, a predictive absorbed dose correctly indicated either good tumor dose coverage or under-dosing of the tumor.ConclusionOur results highlight the predictive value of 99mTc-MAA-based dose estimation to predict non-tumor liver irradiation, which can be applied to prescribe an optimized activity aiming at avoiding liver toxicity. Compared to non-tumoral tissue, a poorer agreement between predicted and measured absorbed dose is observed for tumors.

No-Touch Multi-bipolar Radiofrequency Ablation for the Treatment of Subcapsular Hepatocellular Carcinoma ≤ 5cm Not Puncturable via the Non-tumorous Liver Parenchyma.

The percutaneous ablation of subcapsular hepatocellular carcinoma (S-HCC) may involve a risk of complications such as hemorrhage and tumor seeding, mainly linked to the direct tumor puncture often inevitable with mono-applicator ablation devices. The purpose of this study was to assess the efficacy and safety of no-touch multi-bipolar radiofrequency ablation (NTMBP-RFA) for the treatment of S-HCC ≤ 5cm not puncturable via the non-tumorous liver parenchyma. Between September 2007 and December 2014, 58 consecutive patients (median age: 63years [46-86], nine females) with 59 S-HCC ≤ 5cm (median diameter: 25mm [10-50mm]), not puncturable via the non-tumorous liver parenchyma, were treated with NTMBP-RFA. Response and follow-up were assessed by CT or MRI. Complications were graded using the Cardiovascular and Interventional Radiological Society of Europe classification. Overall local tumor progression (OLTP)-free survival was assessed using the Kaplan-Meier method. A Cox proportional model evaluated the factors associated with OLTP. Signs of peritoneal or parietal tumor seeding were noted during follow-up imaging studies. A complete ablation was achieved in 57/58 patients (98.3%) after one (n = 51) or two (n = 6) procedures. Three patients (5.2%) experienced complications (sepsis, cirrhosis decompensation; CIRSE grade 2 or 3). After a median follow-up period of 30.5months [1-97], no patients had tumor seeding. The 1, 2 and 3-year OLTP-free survival rates were 98%, 94% and 91%, respectively. No factors were associated with OLTP. NTMBP-RFA is a safe and effective treatment for S-HCC not puncturable via the non-tumorous liver parenchyma.

Prediction of Hepatic Parenchymal Change in Gd-EOB-DTPA MR Images after Stereotactic Body Radiation Therapy by Cycle GAN Deep Neural Network

Stereotactic body radiation therapy (SBRT) is known to be an excellent ablative treatment option for small hepatocellular carcinoma (HCC), while possibly deteriorating hepatic function due to inevitable irradiation to surrounding non-tumorous liver parenchyma. A previous work attempted to reveal the threshold dose of parenchymal change after SBRT to be around 20 Gy by analyzing hypo-signal intensity on the hepatobiliary phase (HBP) of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images. However, it found that estimating the parenchymal change is hard as the threshold dose can be patient-specific, ranging from 18 to 33 Gy. Thus, this work proposes to construct a prediction model for the hepatic parenchymal change after SBRT in Gd-EOB-DTPA enhanced MR images by using an image-based deep neural network. The deep learning with convolutional neural network encouraged numerous applications to the image-based prediction. This study aims to build an image-based deep-neural network that predicts the hepatic parenchymal change on HBP in follow-up enhanced MR images by correlating 3-channel input images of pre-treatment enhanced MR, CT and dose images to the output of the follow-up enhanced MR images. The recent advance in deep learning enabled for translating different types of medical imaging modalities by so-called generative adversarial network (GAN). The prediction accuracy could be further enhanced by placing additional generator in reverse direction to be robust to the image misalignment across different imaging modalities, which is named cycle-consistent GAN (cGAN). In this work, the proposed network based on cGAN was trained and tested with 36 and 7 patient cases, respectively. The prediction accuracy was assessed by comparing the predicted and enhanced follow-up MR images in root-mean-squared error (RMSE) and structural similarity (SSIM). For the seven testing cases, the image similarity was measured only inside the manually drawn liver contours, and 5 Gy iso-dose line. Inside the liver contours, the RMSE and SSIM between the reference follow-up MR and predicted MR images from cGAN were 591.21, and 0.9242, which outperformed the results from GAN. For the 5 Gy iso-dose lines, the structural similarity (SSIM) was reduced to 0.6511, which is mainly due to smoothed intensity transition in the predicted MR images. When visually checked, the locations with the signal intensity transition in predicted images correspond to the reference images. The image-based deep neural network with cGAN could possibly predict the hepatic parenchymal change in the follow-up enhanced MR images after SBRT for HCC.Abstract 2305; Table 1Comparison in prediction accuracy of GAN and cGAN deep neural networkLiver Contour>5Gy iso-dose lineRMSESSIMRMSESSIMGAN514.620.6217854.10.9127cGAN350.40.6511623.90.9242 Open table in a new tab

Hepatocellular carcinoma grading and recurrence prediction using T1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging.

The aim of the present study was to explore the value of T1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for grading hepatocellular carcinoma (HCC) and predicting its recurrence rate. A retrospective study was performed that included 75 patients (66 men and 9 women; mean age, 52.89 years; age range, 23–79 years) with HCC who had undergone Gd-EOB-DTPA-enhanced MRI with T1 mapping before surgery. The T1 relaxation time of the 81 lesions and non-tumorous liver parenchyma in 75 patients with HCC were measured before Gd-EOB-DTPA was injected and then at 5, 10 and 20 min after administration, respectively. T1[lesion (L)-hepatic parenchyma (H)]/H (%) was calculated as the increment rate of the T1 value in the lesions relative to the non-tumorous liver parenchyma. One-way analysis of variance and Spearman's correlation analysis was used to compare the differences and relationship of T1 mapping values among the three grades of HCC. A total of 81 lesions were divided into well-differentiated HCC (grades I; n=21), moderately differentiated HCC (grades II; n=40) and poorly differentiated HCC (grades III; n=20) according to the histopathology. The T1(L-H)/H (%) value among grades I, II and III HCC on pre-contrast results and on post-contrast results at the 5-, 10- and 20-min hepatobiliary phase (HBP) were significantly different (P<0.05), and T1(L-H)/H (%) was correlated with the histological grade of HCC at each time point (r=0.637, r=0.554, r=0.499 and r=0.560, respectively, P<0.001). A total of 41 recurrence cases [grade I (n=5), grade II (n=23) and grade III (n=13)] were verified by imaging (CT, MRI or ultrasound) or reoperation. Patients with grade III and grade II HCC had higher recurrence rates compared with that in patients with grade I HCC (P<0.05; median recurrence times were 258 days, 605 days and undefined, respectively). According to the optimal cut-off point for the T1(L-H)/H (%) of the three grades of HCC, patients with HCC in the low T1(L-H)/H (%) value group (≤155.15%) had lower cumulative recurrence rates compared with that in the medium (T1(L-H)/H (%) >155.15% and T1(L-H)/H (%) ≤241.20%) and high (T1(L-H)/H (%) >241.20%) value groups at the 20-min HBP (P<0.05; median recurrence times were undefined, 530 days and 447 days, respectively). These results indicate that the parameters of T1 mapping would be beneficial for predicting the grading and recurrence of HCC.

Histological findings in non-tumoral liver and tumor after chemoembolization with drug-eluting beads

Purpose: To evaluate the histological findings in both tumor and surrounding non-tumoral liver parenchyma after trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) in patients who subsequently underwent hepatectomy.Material and methods: This study included six patients with an HCC (size 15–61 mm). DEB-TACE was performed using polyvinyl alcohol-based hydrogel microspheres loaded with epirubicin. Radiological tumor response was evaluated after DEB-TACE and before hepatectomy, according to the Modified Response Evaluation Criteria in Solid Tumors. Surgical specimens were histologically evaluated with hematoxylin and eosin, and elastic Van Gieson’s staining.Results: Segmental, sub-segmental, or partial hepatectomy were performed 14–58 days after DEB-TACE. There was no remarkable destructive change and minimal to absent inflammatory cell infiltration in the surrounding non-tumoral liver parenchyma. There was no evidence of biliary tract or arterial wall impairment. Complete and partial histological tumor necrosis were found in three cases, respectively, in agreement with the complete and partial responses seen during the radiological evaluation.Conclusion: Histological examination of resected liver specimens after DEB-TACE showed substantial tumor necrosis without any severe inflammatory or destructive changes in the non-tumoral liver parenchyma.

Increased Trimethylation of histone H3K36 associates with biliary differentiation and predicts poor prognosis in resectable hepatocellular carcinoma.

IntroductionTrimethylation of histone H3K36 (H3K36me3), an epigenetic marker of transcription-associated histone modification and stem cell regulation, is expressed in a variety of human cancers. This study elucidated the prognostic significance of H3K36me3 in patients with resectable hepatocellular carcinoma (HCC).MethodsExpression of H3K36me3 was retrospectively evaluated through immunohistochemistry in 152 surgically resected primary HCCs.ResultsIn nontumorous liver parenchyma, H3K36Me3 was detected in bile ducts but not in hepatocytes. H3K36me3 was positive in 104 (68.4%) of the HCCs. Positivity for H3K36me3 was associated with high level of serum α-fetoprotein (>200 ng/mL, P = 0.0148), high tumor grade (P = 0.0017), and high tumor stage (P = 0.0008). Patients with H3K36me3-positive tumors were more likely to have lower 5-year disease-free survival and 5-year overall survival than those with H3K36me3-negative tumors (P = 0.0484 and P = 0.0213, respectively). Multivariate analysis showed that H3K36me3 positivity was an independent predictor of high tumor grade (P = 0.0475) and high tumor stage (P = 0.0114) and thus contributed to poor prognosis. Furthermore, H3K36me3 positivity was significantly correlated with the expression of biliary markers cytokeratin 19 (CK19) and hepatocyte nuclear factor 1β (HNF1β) (P < 0.0001 and P = 0.0005, respectively). Combinatorial analysis revealed that CK19 and HNF1β expression individually exerted additive prognostic adverse effects on HCCs with H3K36me3 positivity.ConclusionsOur study indicates that H3K36me3 positivity is associated with the expression of biliary markers and is a crucial predictor of poor prognosis in resectable HCC.

Preoperative Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Perioperative Liver-Related Complications Following Liver Resection for Colorectal Cancer Metastases.

There are limited data on the potential role of preoperative non-invasive markers, specifically the aspartate-to-alanine aminotransferase ratio and the aspartate aminotransferase-to-platelet ratio index, in predicting perioperative liver-related complications after hepatectomy for colorectal cancer metastases. Patients undergoing liver resection for colorectal cancer metastases in a European institution during 2003-2010 were retrospectively enrolled. Relevant data, such as neoadjuvant chemotherapy, preoperative liver function tests, and perioperative complications, were collected from medical records. The nontumorous liver parenchyma in the surgical specimens of 31 patients was re-evaluated. Overall, 215 patients were included. In total, 40% underwent neoadjuvant chemotherapy and 47% major resection, while 47% had perioperative complications (6% liver-related). In multivariate regression analysis, the aspartate aminotransferase-to-platelet ratio index was independently associated with liver-related complications (odds ratio: 1.149, p = 0.003) and perioperative liver failure (odds ratio: 1.155, p = 0.012). The latter was also true in the subcohort of patients with neoadjuvant chemotherapy (odds ratio: 1.157, p = 0.004) but not in those without such therapy (p = 0.062). The aspartate-to-alanine aminotransferase ratio was not related to liver-related complications (p = 0.929). The area under the receiver operating characteristics curve for the aspartate aminotransferase-to-platelet ratio index as a predictor of liver-related complications was 0.857 (p = 0.008) in patients with neoadjuvant chemotherapy. Increasing aspartate aminotransferase-to-platelet ratio index was observed with an increase in degrees of sinusoidal obstruction syndrome (p = 0.01) but not for fibrosis (p = 0.175) or steatosis (p = 0.173) in the nontumorous liver in surgical specimens. The preoperative aspartate aminotransferase-to-platelet ratio index, but not the aspartate-to-alanine aminotransferase ratio, predicts perioperative liver-related complications following hepatectomy due to colorectal cancer metastases, in particular after neoadjuvant chemotherapy. The aspartate aminotransferase-to-platelet ratio index is related to sinusoidal obstruction syndrome in the nontumorous liver.

The favorable prognosis after operative resection of hypervascular intrahepatic cholangiocarcinoma: A clinicopathologic and immunohistochemical study

The aim of this study was to clarify the clinicopathologic characteristics of hypervascular intrahepatic cholangiocarcinoma (ICC). Seventy patients with a mass-forming type ICC underwent hepatectomy between 2003 and 2013. These patients were divided into 2 groups and compared based on findings during the late arterial phase of computed tomography: hypervascular ICC (the mean computed tomography value of the tumor≥that of the nontumorous liver parenchyma, n=21), and hypovascular ICC (n=49). The overall survival of the hypervascular group was better than that of the hypovascular group (5-year survival: 63% vs 35%, respectively, P=.046). Pathologic examinations showed less lymph node metastasis (0% vs 39%), lymphatic invasion (14% vs 57%), mucin secretion (19% vs 61%), tumor necrosis (24% vs 57%), and combined periductal infiltration (0% vs 27%), P≤.01 each, in the hypervascular group. The microscopic bile ductular feature was more frequent in the hypervascular group (57% vs 29%, P=.023). Immunohistochemical analysis revealed that the hypervascular group had greater immunoreactivity to neural cell adhesion molecule (71% vs 37%, P=.008) and a lesser S100P immunoreactivity (33% vs 73%, P=.002). Multivariate analysis revealed that neural cell adhesion molecule reactivity (P=.018) was independently associated with the hypervascular group. Tumor vascularity predicts the aggressiveness of ICC. In most patients with hypervascular ICC, the tumor has a less invasive nature. Furthermore, the prognosis after resection in patients with hypervascular ICC is significantly better than in patients with hypovascular ICC.

Effect of age on the development of chemotherapy-associated liver injury in colorectal cancer liver metastasis

Introduction: With the lengthening of the average life span, the number of elderly individuals undergoing liver resection for colorectal liver metastasis (CRLM) after chemotherapy has increased. However, the effect of age on the development of chemotherapy-associated liver injury (CALI) in CRLM is unclear. The aim of this study was to clarify the effect of age on the development of CALI in CRLM. Method: Sixty-four patients undergoing liver resection for CRLM after oxaliplatin-based chemotherapy (OBC) were studied. We divided the patients into three groups (A group: < 65 years, B group: 65–74 years, C group: >75 years) according to age at surgery and compared the development rate of CALI between the groups. The patient underwent pathological assessments to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. Results: The A group included 37 cases, B group 17 cases and C group 10 cases. There were no significant differences among the groups regarding the number of OBC cycles and duration of OBC cessation. Sinusoidal injury was observed in 27.0%, 29.4% and 30.0% of the A, B, and C groups, respectively, which was not significantly different (P = 0.479). Steatohepatitis was observed in 35.1%, 35.3% and 40.0% of the A, B, and C groups, respectively, which was not significantly different (P = 0.958). There was no significant correlation between age and sinusoidal pathological score (r = −0.102, P = 0.423) or nonalcoholic fatty liver disease activity score (r < ≤ 0.001, P = 0.997). Conclusions: The development of CALI after OBC in CRLM does not differ according to age.

Changes in portal vein flow mean velocity after glucagon application measured by magnetic resonance imaging flowmetry indicates presence of severe sinusoidal injury in patients with colorectal liver metastases

Aims: Non-invasive methods like aspartate aminotransferase to platelets ratio index (APRI) score or spleen volume changes were proposed to identify patients with sinusoidal injury after preoperative chemotherapies for colorectal liver metastases. Magnetic resonance imaging flowmetry can be used to measure changes in portal vein hemodynamics in patients with sinusoidal injury. The present study evaluates the changes in portal vein flow mean velocity (VELO) after glucagon application and analyzes their ability to predict severe sinusoidal injury (SSI) in comparison to other methods. Methods: Magnetic resonance imaging flowmetry of portal vein was estimated in 28 fasting patients and repeated five minutes after 0.5 mg glucagon injection the day before liver surgery. APRI score was estimated the same day. Spleen volume changes were calculated from segmented spleen volumes on imaging before chemotherapy start and the day before surgery. Resected non-tumorous liver parenchyma was evaluated for sinusoidal injury; parenchymal extinction lesion or nodular regenerative hyperplasia was recognized as SSI. Results: SSI was observed in 6 of 28 patients. Patients with SSI demonstrated higher APRI score 0.65 vs. 0.36, p = 0.028; and non-significant change in spleen volume, 36% vs. 12%, p = 0.764. Percentage of change in VELO five minutes after glucagon in SSI patients was 11% vs. – 3%, p = 0.039. Change in VELO <= – 0.5% predicted SSI with 83% sensitivity and 73% specificity (cross-validated classification error rate 29%), similarly to APRI score >=0.43 with the same sensitivity and specificity but higher classification error rate 32%. Conclusions: Relative changes of VELO five minutes after glucagon administration showed lowered ability of portal system to react on glucagon stimuli in patients with SSI. Application of glucagon as a stress test of portal vein hemodynamic facilitates magnetic resonance imaging flowmetry ability to predict SSI non-invasively.