Combined Hounsfield units of hepatocellular carcinoma on computed tomography and PET as a noninvasive predictor of early recurrence after living donor liver transplantation: Time-to-recurrence survival analysis.

BACKGROUND: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET). METHODS: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points. RESULTS: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96). CONCLUSION: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT.

Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma: The Effectiveness of Different Particle Sizes in Downstaging and Bridging in Living Donor Liver Transplantation.

AIM: To compare the effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) with different particle sizes in bridging and downstaging in pretransplant hepatocellular carcinoma patients. Assess the recurrent and survival rates after living donor liver transplantation (LDLT). METHODS: Retrospective review of 580 patients who underwent TACE using DEB from August 2012 to June 2020 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and post-TACE computed tomography scan images of the liver were reviewed, and treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors criteria. Patients were divided by who met the criteria (n = 342) or beyond (n = 238) the University of California San Francisco criteria for successful bridging and downstaging rate evaluation. Each group was divided into subgroups according to DEB particle sizes (group A: <100µm, group B: 100-300 µm, group C: 300-500 µm, and group D: 500-700 µm) to compare objective response rate and post-LDLT survival rate. RESULTS: Overall successful bridging and downstaging rate is 97.1% and 58.4%, respectively, in the group of patients who meet the criteria (n = 332) and are beyond (n = 139) the University of California San Francisco criteria. Group B (100-300 µm) had a higher successful bridging rate (99.5%, P = .003) and downstaging rate (63.8%, P = .443). This subgroup also demonstrated a higher objective response rate in single (93.2%, P = .038) tumors, multiple (83.3%, P = .001) tumors, and tumors with size less than 5 cm (93.9%, P = .005). There are no significant differences in post-LDLT overall survival rate between different particle sizes. CONCLUSION: TACE with 100 to 300 µm DEB particles is associated with a better chance of bridging and downstaging hepatocellular carcinoma patients to LDLT.

Sarcopenia Affects Liver Regeneration and Long-Term Survival Rate After Living-Donor Liver Transplantation in Patients With Hepatocellular Carcinoma.

PURPOSE: Despite technological and immunologic innovations, some living-donor liver transplant (LDLT) recipients still face poor liver regeneration. Sarcopenia is often recognized as a biomarker for poor outcomes in surgical patients. This study aimed to evaluate associations between sarcopenia and liver regeneration in LDLT recipients. MATERIALS AND METHODS: This retrospective review included consecutive patients who had received LDLT at Chang Gung Memorial Hospital between 2005 and 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. Receiver operating characteristic curve analysis was used to determine the ability of PMI to predict relatively poor survival rates. Correlations between liver regeneration and sarcopenia were evaluated using regression analysis. RESULTS: A total of 109 LDLT recipients were included. The 1-, 3-, 5, 10-, and 15-year survival rates were 93.7%, 84.8%, 79.7%, 74.7%, and 73.3% in males and 93.3%, 83.3%, 83.3%, 71.4%, and 71.4% in females. PMIs were significantly different based on 10- and 15-year overall survival rates (P = .001 and P = .000) in male patients. Receiver operating characteristic curve analysis revealed the PMI cutoff point at 6.7 cm2/m2 (sensitivity = 48.3%, specificity = 81%, AUC (area under the ROC curve) = 0.685) based on 10-year survival. Linear regression analysis revealed that PMI was significantly associated with liver regeneration in males (P = .013). CONCLUSIONS: Sarcopenia and low PMI are associated with poor liver regeneration and long-term survival after LDLT in male patients. Further studies, including sarcopenia with conventional scores, may help to more reliably predict liver regeneration and mortality among LDLT patients with hepatocellular carcinoma.

Portal Dynamics After Living Donor Liver Transplant in Pediatric Recipients: A 10-Year Follow-Up Retrospective Study.

BACKGROUND: It may be difficult for pediatric patients to evaluate the impact of liver transplantation (LT) on splenomegaly due to the natural growth course. The long-term dynamics of portal vein (PV) size and PV flow after LT in pediatric patients are unclear. We aimed to evaluate the long-term transition of the splenic size, PV size, and PV flow velocity in pediatric patients who underwent successful living donor liver transplantation (LDLT) and survived >10 years. METHODS: From October 2004 to December 2010, 39 pediatric patients (25 boys; 14 girls) underwent LDLT, received pre-LDLT and post-LDLT computed tomography scans and long-term ultrasound sonography follow-up, and survived >10 years without additional intervention at our institution. We analyzed the short- to mid-term and long-term impact of LDLT on splenic size, PV size, and PV flow velocity over time. RESULTS: The PV diameter increased throughout the 10-year follow-up (P < .001). The PV flow velocity increased 1 day after LDLT (P< .001); proceeded to decrease 3 days after LDLT, reaching a low point 6 to 9 months after LDLT; and remained stable throughout the 10-year follow-up. Regression of the splenic volume at 6 to 9 months after LDLT (P < .001) was noted. However, the splenic size steadily increased on long-term follow-up. CONCLUSIONS: Although LDLT has a significant short-term reduction effect on splenomegaly, the long-term transitional trend of the splenic size and PV diameter may increase along with children's growth. The PV flow reached a stable status 6 to 9 months after LDLT and remained so until 10 years after LDLT.

Usefulness of controlled attenuation parameter in monitoring clinically relevant decline of hepatic steatosis for non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is the reference standard of hepatic steatosis assessment. This study evaluates usefulness of controlled attenuation parameter (CAP) in monitoring the clinically relevant outcome by MRI-PDFF for non-alcoholic fatty liver disease (NAFLD) patients. METHODS: NAFLD patients were enrolled prospectively. Instruction was given in lifestyle modifications with exercise and control of metabolic factors. MRI-PDFF and CAP were performed at enrollment and follow-up, with the diagnostic validity of CAP in monitoring clinically relevant outcome defined as a decline of ≥30% relative to baseline value by MRI-PDFF. RESULTS: A total of 75 patients (male/female: 49/26, mean age: 53.2) were enrolled. Baseline MRI-PDFF, CAP and liver stiffness was 14.4%, 300.2 dB/m and 6.5 kPa. In a median interval of 369 days, thirteen (17.3%) patients achieved clinically relevant outcome with decline of 46.7 dB/m by CAP, compared with increase of 5.1 in the other patients. In multivariate analysis, clinically relevant outcome was associated with changes (Δ) of CAP and glucose. Assessed by area under receiver operating curve, the performances of ΔCAP in predicting clinically relevant outcome were 0.815 and 0.808, and with the specificity of >90%, the ΔCAP cutoff was -46 dB/m and -15% relative to baseline value; sensitivity was 53.8% and 46.2% with negative predictive value of 90.3% and 88.9% respectively. CONCLUSIONS: For NAFLD patients, CAP exhibited good performance in monitoring clinically relevant decline of hepatic steatosis in MRI-PDFF. With the cutoffs of -46 dB/m or -15%, ΔCAP is useful in excluding clinical relevant outcome achievement.

Efficacy and Safety of Combined Ethanol-Lipiodol Mixture and Drug-Eluting Bead TACE for Large HCC.

Purpose: To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor >8 cm or multiple tumors with the largest tumor diameter >5 cm and total tumor diameter >10 cm. Patients and Methods: Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03-34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP >400 ng/mL (p = 0.0306), maximum tumor size >10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy. Conclusion: Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.

Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma.

Background: The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. Methods: From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Results: Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Conclusion: Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.

Efficacy and safety of splenic artery embolization for intractable ascites using Amplatzer vascular plug versus coil after living donor liver transplantation.

PURPOSE Intractable ascites (IA) is an uncommon but challenging complication after liver transplantation. Splenic artery embolization (SAE) modulates the splenic artery and regulates portal flow. This study aimed to evaluate the efficacy and safety of SAE using the Amplatzer vascular plug (AVP) versus coil embolization for post-living-donor liver transplantation (LDLT) IA. METHODS This retrospective study evaluated consecutive patients from 1 center who received LDLT (n=1410) between March 2006 and August 2019. The inclusion criteria for SAE were splenomegaly with IA after LDLT. RESULTS Totally 15 patients underwent SAE for post-LDLT IA. Eleven patients who received AVP embolization (age, 51.2 ± 15.1 years; range, 8-63 years; 5 men and 6 women) were compared with 4 patients receiving coil embolization (age, 30.8 ± 30.8 years; range, 1.5-63 years; 2 men and 2 women). AVP and coil embolization both significantly reduced portal vein hyperflow (plug/ coil; P <.001/.006) and decreased ascites volume (plug/coil; P <.003/.042). The benefits of AVP embolization included shorter procedure time (P =.029), significantly reduced splenic volume (P =.012), increased liver volume (P =.012), decreased spleen/liver ratio (P =.012), and improvement of pancytopenia (P =.008) due to secondary hypersplenism. No significant differences were found between the two groups in the length of hospital stay or complications such as splenic infarction, pancreatitis, or sepsis. CONCLUSION SAE using AVP and coil embolization provide effective and safe methods for managing patients with IA after LDLT. AVP embolization may be more efficient than coil embolization, providing more effective reduction of ascites volume and the advantages of shortened procedure time and improvement of hypersplenism.

Development of Novel Residual-Dense-Attention (RDA) U-Net Network Architecture for Hepatocellular Carcinoma Segmentation.

The research was based on the image recognition technology of artificial intelligence, which is expected to assist physicians in making correct decisions through deep learning. The liver dataset used in this study was derived from the open source website (LiTS) and the data provided by the Kaohsiung Chang Gung Memorial Hospital. CT images were used for organ recognition and lesion segmentation; the proposed Residual-Dense-Attention (RDA) U-Net can achieve high accuracy without the use of contrast. In this study, U-Net neural network was used to combine ResBlock in ResNet with Dense Block in DenseNet in the coder part, allowing the training to maintain the parameters while reducing the overall recognition computation time. The decoder was equipped with Attention Gates to suppress the irrelevant areas of the image while focusing on the significant features. The RDA model was used to identify and segment liver organs and lesions from CT images of the abdominal cavity, and excellent segmentation was achieved for the liver located on the left side, right side, near the heart, and near the lower abdomen with other organs. Better recognition was also achieved for large, small, and single and multiple lesions. The study was able to reduce the overall computation time by about 28% compared to other convolutions, and the accuracy of liver and lesion segmentation reached 96% and 94.8%, with IoU values of 89.5% and 87%, and AVGDIST of 0.28 and 0.80, respectively.

A Scoring System for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Quantitative Functional MRI.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a histopathological marker and risk factor for HCC recurrence. We integrated diffusion-weighted imaging (DWI) and magnetic resonance (MR) image findings of tumors into a scoring system for predicting MVI. In total, 228 HCC patients with pathologically confirmed MVI who underwent surgical resection or liver transplant between November 2012 and March 2021 were enrolled retrospectively. Patients were divided into a right liver lobe group (n = 173, 75.9%) as the model dataset and a left liver lobe group (n = 55, 24.1%) as the model validation dataset. Multivariate logistic regression identified two-segment involved tumor (Score: 1; OR: 3.14; 95% CI: 1.22 to 8.06; p = 0.017); ADCmin ≤ 0.95 × 10-3 mm2/s (Score: 2; OR: 10.88; 95% CI: 4.61 to 25.68; p = 0.000); and largest single tumor diameter ≥ 3 cm (Score: 1; OR: 5.05; 95% CI: 2.25 to 11.30; p = 0.000), as predictive factors for the scoring model. Among all patients, sensitivity was 89.66%, specificity 58.04%, positive predictive value 68.87%, and negative predictive value 84.41%. For validation of left lobe group, sensitivity was 80.64%, specificity 70.83%, positive predictive value 78.12%, and negative predictive value 73.91%. The scoring model using ADCmin, largest tumor diameter, and two-segment involved tumor provides high sensitivity and negative predictive value in MVI prediction for use in routine functional MR.

Non-Contrast-Enhanced and Contrast-Enhanced Magnetic Resonance Angiography in Living Donor Liver Vascular Anatomy.

Background: Since the advent of a new generation of inflow-sensitive inversion recovery (IFIR) technology, three-dimensional non-contrast-enhanced magnetic resonance angiography is being used to obtain hepatic vessel images without applying gadolinium contrast agent. The purpose of this study was to explore the diagnostic efficacy of non-contrast-enhanced magnetic resonance angiography (non-CE MRA), contrast-enhanced magnetic resonance angiography (CMRA), and computed tomography angiography (CTA) in the preoperative evaluation of living liver donors. Methods: A total of 43 liver donor candidates who were evaluated for living donor liver transplantation completed examinations. Donors' age, gender, renal function (eGFR), and previous CTA and imaging were recorded before non-CE MRA and CMRA. CTA images were used as the standard. Results: Five different classifications of hepatic artery patterns (types I, III, V, VI, VIII) and three different classifications of portal vein patterns (types I, II, and III) were identified among 43 candidates. The pretransplant vascular anatomy was well identified using combined non-CE MRA and CMRA of hepatic arteries (100%), PVs (98%), and hepatic veins (100%) compared with CTA images. Non-CE MRA images had significantly stronger contrast signal intensity of portal veins (p < 0.01) and hepatic veins (p < 0.01) than CMRA. No differences were found in signal intensity of the hepatic artery between non-CE MRA and CMRA. Conclusion: Combined non-CE MRA and CMRA demonstrate comparable diagnostic ability to CTA and provide enhanced biliary anatomy information that assures optimum donor safety.

Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Living Donor Liver Transplant.

BACKGROUND: Gadolinium-ethoxybenzyl-diethylene triamine pentaacetic acid (Gd-EOB-DTPA) is a newer magnetic resonance contrast that has the combined effect of conventional and liver-specific contrast. The use of Gd-EOB-DTPA may aid in management of patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplant (LDLT). MATERIALS AND METHODS: We retrospectively reviewed all HCC patients who received LDLT with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as part of a pretransplant evaluation between October 2012 and October 2016. The detection rate and impact on decision making were assessed between multidetector-row computed tomography (MDCT) and Gd-EOB-DTPA-enhanced MRI with pathology of the explanted liver being the reference standard. RESULTS: We analyzed 25 patients with 80 nodules. Gd-EOB-DTPA-enhanced MRI showed superior detection rate for HCCs than MDCT (76.1% vs 35.8%). Among the 25 patients, 16 had additional HCCs detected by Gd-EOB-DTPA-enhanced MRI, which led to changes in therapeutic decisions in 11 patients. The recurrence rate and mortality rate were 4% (1 of 25). In the same period in our institution, the mortality rate was 13.9% (25 of 180) for those who did not receive Gd-EOB-DTPA-enhanced MRI as part of the pretransplant evaluation. CONCLUSIONS: The use of Gd-EOB-DTPA-enhanced MRI can aid in characterization of indeterminate nodules and detect more HCCs and thus more adequate downstaging and pretransplant neoadjuvant treatment ensue, which may lower the recurrence rate after LDLT.

Portosystemic Shunt in Pediatric Living Donor Liver Transplant.

BACKGROUND: To evaluate the significance of portosystemic shunts and associated long-term outcomes in living donor liver transplant (LDLT) among pediatric patients. METHODS: Retrospective review of 121 pediatric patients who underwent LDLT between May 1994 and December 2015 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and postoperative computed tomography images of the liver were reviewed, and portal vein complications were assessed. RESULTS: Ninety-seven pediatric patients were included in the study, and 70 had portosystemic shunts before transplant. Thirty-three patients have portal systemic shunt (PSS) 6 months after transplant (mean [SD] shunt size, 4.59 [1.98] mm). Thirty-seven patients' portosystemic shunts closed spontaneously (mean [SD] shunt size, 3.14 [1.06] mm). Smaller PSSs tend to close spontaneously with a cutoff point of 3.35 mm by receiver operating characteristic curve (P = .01). Patients with PSS have more portal vein complications than those without PSS (44.3% vs 11.1%, P = .02). Among PSS recipients, patients with portal vein complications tend to have larger PSS size (mean [SD], 4.14 [1.96] mm vs 3.59 [1.48] mm), although the difference is not statistically significant (P = .19). CONCLUSIONS: In pediatric patients, preoperative portosystemic shunts are significantly correlated with portal venous complications, some of which require minimal interventions after LDLT with good outcomes. Shunts larger than 3.35 mm tend to persist after transplant with increased portal venous complications.

Sarcopenia adversely impacts postoperative complications in living-donor liver transplantation recipients.

Despite technological and immunological innovations, living-donor liver transplant (LDLT) recipients still face substantial risk of postoperative complications. Sarcopenia is being recognized more and more as a biomarker that correlates with poor outcomes in surgical patients. The purpose of this study was to evaluate the relationship between sarcopenia and significant surgical complications in LDLT recipients. This retrospective review included patients who had received LDLT at our institute from 2005 to 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. ROC curve analysis was used to determine the ability of PMI to predict postoperative complications. Correlations between major postoperative complications and sarcopenia were evaluated using regression analysis. A total of 271 LDLT recipients were included. No significant differences were found between PMI and major postoperative complications in male patients. Female recipients with major postoperative complications had significantly lower mean PMI values (P = 0.028), and the PMI cut-off value was 2.63 cm2/m2. Postoperative massive pleural effusion requiring pigtail drainage occurred more frequently in the sarcopenia group than in the non-sarcopenia group (P = 0.003). 1-, 3-, 5- and 10-year overall survival rates in female were significantly poorer in the sarcopenia group (n = 14) compared with the non-sarcopenia group (n = 108), at 92.9% versus 97.2%, 85.7% versus 95.4%, 85.7% versus 92.5% and 70.1 versus 82.0%, respectively (P = 0.041) and 94.6%, 89.9%, 85.9% and 78.5% in male patients. Sarcopenia is associated with a significantly higher risk of major postoperative complications in females. PMI and sarcopenia together are predictive of major postoperative complications and survival rates in female LDLT recipients.

Recognition Rate Advancement and Data Error Improvement of Pathology Cutting with H-DenseUNet for Hepatocellular Carcinoma Image.

Due to the fact that previous studies have rarely investigated the recognition rate discrepancy and pathology data error when applied to different databases, the purpose of this study is to investigate the improvement of recognition rate via deep learning-based liver lesion segmentation with the incorporation of hospital data. The recognition model used in this study is H-DenseUNet, which is applied to the segmentation of the liver and lesions, and a mixture of 2D/3D Hybrid-DenseUNet is used to reduce the recognition time and system memory requirements. Differences in recognition results were determined by comparing the training files of the standard LiTS competition data set with the training set after mixing in an additional 30 patients. The average error value of 9.6% was obtained by comparing the data discrepancy between the actual pathology data and the pathology data after the analysis of the identified images imported from Kaohsiung Chang Gung Memorial Hospital. The average error rate of the recognition output after mixing the LiTS database with hospital data for training was 1%. In the recognition part, the Dice coefficient was 0.52 after training 50 epochs using the standard LiTS database, while the Dice coefficient was increased to 0.61 after adding 30 hospital data to the training. After importing 3D Slice and ITK-Snap software, a 3D image of the lesion and liver segmentation can be developed. It is hoped that this method could be used to stimulate more research in addition to the general public standard database in the future, as well as to study the applicability of hospital data and improve the generality of the database.

Sustained-Release and pH-Adjusted Alginate Microspheres-Encapsulated Doxorubicin Inhibit the Viabilities in Hepatocellular Carcinoma-Derived Cells.

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4-by-5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~39 µm) across five groups with different alginate: NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loading %. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate: NaHCO3 = 1 exhibited rough and porous surfaces, high Young's modulus, and hardness. In each group with the same alginate: NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relatively high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relatively high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relatively high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

In-Series U-Net Network to 3D Tumor Image Reconstruction for Liver Hepatocellular Carcinoma Recognition.

Cancer is one of the common diseases. Quantitative biomarkers extracted from standard-of-care computed tomography (CT) scan can create a robust clinical decision tool for the diagnosis of hepatocellular carcinoma (HCC). According to the current clinical methods, the situation usually accounts for high expenditure of time and resources. To improve the current clinical diagnosis and therapeutic procedure, this paper proposes a deep learning-based approach, called Successive Encoder-Decoder (SED), to assist in the automatic interpretation of liver lesion/tumor segmentation through CT images. The SED framework consists of two different encoder-decoder networks connected in series. The first network aims to remove unwanted voxels and organs and to extract liver locations from CT images. The second network uses the results of the first network to further segment the lesions. For practical purpose, the predicted lesions on individual CTs were extracted and reconstructed on 3D images. The experiments conducted on 4300 CT images and LiTS dataset demonstrate that the liver segmentation and the tumor prediction achieved 0.92 and 0.75 in Dice score, respectively, by as-proposed SED method.

Transarterial Chemoembolization Using 100-µm Drug-Eluting Microspheres in Patients with Hepatocellular Carcinoma: A Prospective Study and Midterm Follow-up.

PURPOSE: The purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres. MATERIALS AND METHODS: Between October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-µm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile. RESULTS: Median follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff). CONCLUSIONS: Tandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation.

Intensive Doppler Ultrasonography for Early Detection of Hepatic Artery Thrombosis After Adult Living Donor Liver Transplantation.

BACKGROUND Early hepatic artery thrombosis (eHAT) is a severe arterial complication leading to biliary complications and graft failure in living donor liver transplantation (LDLT). This study sought to early identify the abnormal waveforms of eHAT by using intensive Doppler ultrasonography (DUS) after LDLT and to assess the clinical outcome in these eHAT patients. MATERIAL AND METHODS DUS for 419 adult LDLT recipients was performed twice after vascular anastomosis during liver transplantation and once a day at the bedside for at least 2 weeks. RESULTS Nine adult LDLT recipients with eHAT were identified by using bedside DUS with subsequent computed tomography angiography (CTA). All eHAT cases were noted in the first 2 weeks. Five patients with CTA findings of partial thrombus with the small visualized intrahepatic hepatic artery (HA) were treated with intravenous thrombolysis (IVT) (medical group). Another 4 patients with CTA findings of extrahepatic HA occlusion and nonvisualization of intrahepatic HAs were treated by arterial re-anastomosis (surgical group). The prevalence of long-term non-anastomotic biliary strictures was 33.3% in the surgical group. Intensive post-LDLT DUS is a convenient and sensitive tool for eHAT detection. CONCLUSIONS Subsequent CTA gives valid information on occluded arteries and associated findings, which impact decision-making and are correlated with patient outcome. Our protocol of DUS has high sensitivity and diagnostic accuracy for use in in eHAT patients with partial occlusion, and it can be applied for IVT treatment, avoiding the need for reoperation and preventing long-term biliary complications.

Management of Biliary Stricture in Pediatric Living Donor Liver Transplantation Recipients.

OBJECTIVE: Evaluation of the efficiency of percutaneous transhepatic cholangial drainage (PTCD) for biliary stricture after living donor liver transplantation (LDLT) in pediatric patients. MATERIALS AND METHODS: We retrospectively analyzed biliary stricture observed in pediatric biliary atresia. LDLT patients were studied between June 1994 and November 2017. A total of 291 patients were observed, 10 of whom were found to have biliary strictures. RESULTS: Among the 291 patients, we observed 10 patients with biliary stricture, which were divided into 2 groups: group A were patients who have biliary stricture with vascular complication (n = 4), and group B were patients who have biliary stricture without vascular complication (n = 4). Two children without vascular complications received PTCD to bridge the time for Rou-en-Y hepaticojejunostomy. A total of 12 procedures were carried out: only 1 patient (10%) underwent the procedure 3 times. The average interval between liver transplantation and percutaneous transhepatic drainage was 63.2 months in group A and 156.9 months in group B, and no significant difference between the 2 groups (P = .127). Clinical success was achieved in all patients. The PTCD was removed from 3 of 4 patients (75%) in group B with clinical success at a mean follow-up of 32.2 months. Higher PTCD removal rate (75%, P < .05) was found in the patients without vascular complication. All of the patients in group A were tube dependent during follow-up. No major complications were observed among all procedures. CONCLUSION: PTCD is an effective rescue therapy in pediatric LDLT patients, especially in nonvascular complication patients. Successful internal-external drainage and stenting can prevent a second operation for bile duct reconstruction.