SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.

Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.

Lifestyle Modification Leads to Spatially Variable Reduction in Hepatic Steatosis in Potential Living Liver Donors.

The spatial variability of hepatic fat reduction in potential living liver donors with hepatic steatosis (HS) who undergo lifestyle modification has not been investigated. Here, we aimed to examine the intrasegmental and intersegmental variability of changes in liver attenuation on computed tomography (CT) in potential living liver donors with HS after diet modification and exercise. A total of 87 living liver donor candidates (30.5 ± 7.0 years; 74 males) with biopsy-proven macrovesicular fat (MaF) ≥10% were included. All underwent diet modification and exercise to improve HS, baseline and follow-up unenhanced CT scans, and liver biopsies. Attenuation and its variability (mean and standard deviation, respectively, in Hounsfield units) in segmental, lobar, superficial, deep, and whole areas of the liver were measured across 32 different regions of interest on both baseline and follow-up CT. At baseline, the right lobe and superficial areas of liver showed significantly lower and more variable attenuation than left lobe and deep areas. Greater variability was noted in patients with more severe HS. Mean interval changes in liver attenuation and variability before and after diet modification and exercise were 13.7 (range, -10.6 to 46.2) and 4.7 (1.6-10.6), respectively. The mean interval change in liver attenuation was significantly higher in the right lobe than in the left (14.7 versus 12.7; P < 0.001), and in superficial areas than in deep areas (14.0 versus 13.4; P = 0.02). Greater variability and larger interval changes in liver attenuation were noted in those who responded (≥20% decrease in MaF) to diet modification and exercise than in those who did not. In conclusion, potential living liver donors with HS show significant intrasegmental and intersegmental variability in hepatic fat reduction on CT before and after diet modification and exercise.

Long-term perioperative outcomes of pure laparoscopic liver resection versus open liver resection for hepatocellular carcinoma: a retrospective study.

BACKGROUND: Laparoscopic treatment for hepatocellular carcinoma (HCC) has increased. We retrospectively compared the perioperative and long-term oncological outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) in well-matched patient groups using propensity score matching (PSM). METHODS: We reviewed medical records of patients with HCC who underwent liver resection between July 2007 and April 2016 at our center. In total, 2335 patients were included in this study and divided into LLR (n = 264) and OLR (n = 2071) groups. For group comparisons, 1:2 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures. RESULTS: After PSM, there were 217 and 434 patients in the LLR and OLR groups, respectively. The LLR group had shorter hospital stays (8.9 vs. 14.8 days; P < 0.001) and lower postoperative morbidity (6.5% vs. 12.0%; P = 0.022). The 1-, 3-, and 5-year overall survival rates were 98.1%, 87.0%, and 78.6%, respectively, for the LLR group, and 98.3%, 90.8%, and 84.3%, respectively, for the OLR group (P = 0.570). The 1-, 3-, and 5-year disease-free survival rates were 81.0%, 62.0%, and 49.1%, respectively, for the LLR group, and 85.3%, 64.7%, and 56.2%, respectively, for the OLR group (P = 0.563). CONCLUSIONS: Long-term oncological outcomes were comparable between LLR and OLR for selected patients. LLR was associated with multiple benefits, even for selected patients with cirrhosis who underwent major hepatectomy. LLR for HCC performed by an experienced surgeon could be considered a safe and feasible alternative to OLR for selected patients.

Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death. METHODS: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016. RESULTS: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM. CONCLUSION: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

Clinical Guidance for Point-of-Care Ultrasound in the Emergency and Critical Care Areas after Implementing Insurance Coverage in Korea.

Point-of-care ultrasound (POCUS) is a useful tool that is widely used in the emergency and intensive care areas. In Korea, insurance coverage of ultrasound examination has been gradually expanding in accordance with measures to enhance Korean National Insurance Coverage since 2017 to 2021, and which will continue until 2021. Full coverage of health insurance for POCUS in the emergency and critical care areas was implemented in July 2019. The National Health Insurance Act classified POCUS as a single or multiple-targeted ultrasound examination (STU vs. MTU). STU scans are conducted of one organ at a time, while MTU includes scanning of multiple organs simultaneously to determine each clinical situation. POCUS can be performed even if a diagnostic ultrasound examination is conducted, based on the physician's decision. However, the Health Insurance Review and Assessment Service plans to monitor the prescription status of whether the POCUS and diagnostic ultrasound examinations are prescribed simultaneously and repeatedly. Additionally, MTU is allowed only in cases of trauma, cardiac arrest, shock, chest pain, and dyspnea and should be performed by a qualified physician. Although physicians should scan all parts of the chest, heart, and abdomen when they prescribe MTU, they are not required to record all findings in the medical record. Therefore, appropriate prescription, application, and recording of POCUS are needed to enhance the quality of patient care and avoid unnecessary cut of medical budget spending. The present article provides background and clinical guidance for POCUS based on the implementation of full health insurance coverage for POCUS that began in July 2019 in Korea.

Point-of-Care Ultrasound Could Streamline the Emergency Department Workflow of Clinically Nonspecific Intussusception.

OBJECTIVES: The aim of this study was to evaluate whether point-of-care ultrasound (POCUS) for intussusception screening streamlines the workflow of clinically nonspecific intussusception (CNI), an intussusception presenting with only 1 manifestation of the classic triad, and/or vomiting. METHODS: We reviewed 274 consecutive children with intussusception, aged 6 years or younger, who visited a tertiary care hospital emergency department between May 2012 and April 2016. This period was dichotomized by May 2014 (the "PRE" and "POST" groups), starting point of implementation of the POCUS protocol for intussusception screening. All children with CNI who had positive results on or forwent POCUS underwent radiologist-performed ultrasound (US). We measured and compared emergency department length of stay (EDLOS), the sum of door-to-reduction and observation times, and the frequency of POCUS and positive US results between the 2 groups. RESULTS: Of 160 children with CNI, 93 visited the emergency department since May 2014. The POST group showed a shorter median EDLOS (856 vs 630 minutes, P < 0.001), door-to-reduction time (137 vs 111 minutes, P = 0.002), and observation time (700 vs 532 minutes, P < 0.001). The POST group had a higher frequency of POCUS (12% vs 60%, P < 0.001) with positive US results (33% vs 59%, P < 0.001). The PRE group had a higher frequency of severe bowel edema (16% vs 1%, P < 0.001). No significant differences were found in the severity, recurrence, admission, and surgery. One child had a false-negative result on POCUS. CONCLUSIONS: Point-of-care ultrasound could streamline the workflow of CNI via decrease in EDLOS and unnecessary referrals for US.

Implications of Increased Weight Status for the Occurrence of Fall-Induced Intracranial Hemorrhage in Children Aged 4 Years or Younger.

OBJECTIVES: The aim of this study was to investigate the association between increased weight status (IWS), a weight for age/sex at greater than the 95th percentile, and fall-induced intracranial hemorrhage (ICH) in children aged 4 years or younger. METHODS: In 7072 children aged 4 years or younger with head injury who visited a tertiary care hospital emergency department in Korea from 2013 through 2015, the presence of fall-induced ICH was reviewed. The association between IWS and ICH was investigated by multivariable logistic regression. We retrospectively validated the Pediatric Emergency Care Applied Research Network rule alone and in combination with IWS for predicting ICH. RESULTS: Of 7072 children, 547 (7.7%) underwent computed tomography, of whom 451 (6.4%) were enrolled. Of these, 41 (9.1%; estimated event rate, 0.6%) had ICHs, and 26 (5.8%) had IWS. Increased weight status was more common in the children with ICH (P = 0.023). The association between IWS and ICH remained significant after adjustment (odds ratio, 5.24; 95% confidence interval [CI], 1.49-18.46; P = 0.010). The validation of the rule in combination with IWS showed no significant increases in a sensitivity (92.7% [95% CI, 80.1%-98.5%] to 95.7% [95% CI, 83.5%-99.4%]) and negative predictive value (98.2% [95% CI, 94.7%-99.4%] to 98.8% [95% CI, 95.4%-99.8%]). CONCLUSIONS: Increased weight status is associated with fall-induced ICH in children aged 4 years or younger. Information on weight status could be potentially helpful in predicting ICH in young children with fall-induced head injury.

Diagnostic Performance for Hepatic Artery Occlusion After Liver Transplantation: Computed Tomography Angiography Versus Contrast-Enhanced Ultrasound.

The purpose of this study was to compare the diagnostic performance of computed tomography angiography (CTA) and contrast-enhanced ultrasound (CEUS) when used to diagnose significant hepatic artery occlusion (HAO) in patients that was suspected on Doppler ultrasound (US). Among 3465 adult liver transplantations (LTs) performed between January 2010 and February 2018, 329 recipients were suspected of having HAO by Doppler US. In these patients, 139 recipients who had undergone both CTA and CEUS as second-line studies were included. CTA and CEUS were retrospectively reviewed using the criteria for HAO used in previous studies (CTA, ≥50% stenosis at the anastomosis; CEUS, no HA enhancement or delayed and discontinuous enhancement). The diagnostic values of CTA and CEUS were compared using the McNemar test. CEUS showed statistically significant better accuracy and specificity than CTA in patients with Doppler US abnormality seen after LT (accuracy, 99.3% versus 89.2%, P < 0.001; specificity, 100% versus 83.1%, P < 0.001). CTA had 15 false-positive diagnoses, and CEUS had 1 false-negative diagnosis. In conclusion, CEUS showed higher specificity and positive predictive value than CTA for the diagnosis of HAO in selected patients with a Doppler US abnormality. However, even if there is no HAO diagnosed on CEUS, continuous monitoring and follow-up imaging are required when HAO is strongly suspected in the clinical setting and on CTA.

Clinical usefulness of gadoxetic acid-enhanced MRI for evaluating biliary anatomy in living donor liver transplantation.

OBJECTIVES: To determine the incremental value of hepatobiliary-phase-MRC (HBP-MRC) added to T2-magnetic resonance cholangiography (T2-MRC) for evaluating biliary anatomy in living donor liver transplantation (LDLT) and to correlate T2+HBP-MRC findings with surgical results. METHODS: A total of 276 donors who underwent T2 and gadoxetic acid-enhanced MRI before right hemihepatectomy for LDLT between January and December 2016 were retrospectively enrolled. Two reviewers evaluated biliary anatomy classification using T2-MRC in the first session and T2+HBP-MRC in the second session. The sensitivity, specificity, and confidence level (5-point scale) of T2-MRC and T2+HBP-MRC for variant biliary anatomy were evaluated. The agreement rates between MRC and operative cholangiography for each biliary anatomy classification and the underestimation rates for multiple bile duct openings (BDOs) for both MRC techniques were evaluated. RESULTS: Of the 276 donors, variant biliary anatomy was observed in 36.2% (100/276). T2+HBP-MRC showed a significantly higher sensitivity for diagnosing variant biliary anatomy than T2-MRC alone (99.0% [99/100] vs. 89.0% [89/100], p = 0.006), with better observer confidence level (4.9 ± 0.3 vs. 4.6 ± 0.7, p < 0.001) and inter-observer agreement (kappa, 0.902 vs. 0.730). Compared with T2-MRC alone, T2+HBP-MRC provided significantly higher agreement with operative cholangiography in biliary anatomy classification (98.6% [272/276] vs. 89.9% [248/276], p < 0.001), and significantly lower underestimation rate for multiple BDOs (5.8% [16/276] vs. 9.4% [26/276], p = 0.002). CONCLUSION: T2+HBP-MRC might be considered than T2-MRC alone, as a better depiction of biliary anatomic variations, correlated with surgical findings. KEY POINTS: •T2+HBP-MRC predicted variant biliary anatomy more accurately than T2-MRC alone. •T2+HBP-MRC might have clinical usefulness by reducing the underestimation rate of multiple bile duct openings, which requires more complicated biliary anastomoses.

CT of acute rejection after liver transplantation: a matched case-control study.

PURPOSE: This study was conducted in order to investigate computed tomography (CT) findings associated with acute cellular rejection (ACR) following liver transplantation (LT) and their relevance to clinical outcomes. MATERIALS AND METHODS: We analyzed 120 patients with newly diagnosed ACR following LT for various liver diseases and 119 controls matched for age, sex, type of liver graft, and date of CT exam following LT. Two radiologists analyzed the images for morphological characteristics of the graft, morphological change in the major draining vein, graft enhancement in the portal venous phase, graft attenuation on noncontrast CT, and periportal halo. Univariate analysis was used to determine the association between radiological findings and ACR. Clinical outcomes, including treatment response and graft survival, were compared between patients with and without associated radiological findings. RESULTS: Morphological characteristics of the graft (i.e., globular swelling), morphological change in the major draining vein (i.e., nonanastomotic luminal narrowing), and heterogeneous enhancement were significantly associated with ACR (all p < 0.001). On univariate analysis, the severity of morphological characteristics of the grafts (mild/severe: odds ratio [OR], 19.98/32.24) and morphological change in the major draining vein (without/with prestenotic dilatation: OR, 4.17/22.5) were significantly associated with the increased possibility of an ACR diagnosis. Clinical outcomes for treatment response and graft survival were not significantly different between patients with and without associated radiological findings. CONCLUSIONS: Globular swelling, nonanastomotic stenosis with or without prestenotic dilatation of the major draining vein, and heterogeneous enhancement of the graft on portal venous-phase CT were significantly associated with ACR. KEY POINTS: • Globular swelling of the graft, nonanastomotic narrowing in the major vein, and heterogeneous graft enhancement on CT were significantly associated with acute cellular rejection (ACR). • Associated CT findings were highly specific but not sensitive for differentiating ACRs from matched controls.

Splenic devascularization can replace splenectomy during adult living donor liver transplantation - a historical cohort study.

Simultaneous splenectomy (SSPX) in adult living donor liver transplantation (ALDLT) has definitely beneficial roles such as portal flow modulation in small-for-size graft and correction of hypersplenism-related pancytopenia, and so on, but disastrous complications after SSPX often occur. For the first time, we devised unique and innovative splenic devascularization (SDV) procedure to alleviated untoward effects of SSPX but to maintain its benefits for the indicated patients. From April 2013 to December 2014, 520 recipients underwent ALDLT, and the SSPX and SDV were simultaneously performed in 62 (11.9%) and 61 (11.7%) patients, respectively. The most common indication was hypersplenism-related pancytopenia (n = 101), small-for-size graft (n = 14), hepatitis C virus (HCV) (n = 7), and splenic artery aneurysm (n = 1). Postoperative small-for-size graft syndrome (SFSS) was absent in both SSPX and SDV, and preoperative pancytopenia was improved in both groups since postoperative 1 week, although SSPX was more substantial than SDV. Preoperative splenic volume (706.2 ± 282.9 ml) after SDV significantly decreased to 425.5 ± 204.4 ml on 1 month, respectively. In contrast to SDV, SSPX resulted in longer operation time and higher incidence of postoperative complications including mortality. In conclusion, SDV can replace SSPX during ALDLT without hampering its beneficial roles seriously, but get rid of splenectomy-related lethal complication.

Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.

The Evolving Role of CD8+CD28- Immunosenescent T Cells in Cancer Immunology.

Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized-tolerance, anergy, exhaustion, and senescence-CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28- senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28- senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.

Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Living-donor liver transplantation (LDLT) can simultaneously cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving long-term results in patients with HCC. ABO-incompatible LDLT could expand the living-donor pool, reduce waiting times for deceased-donor liver transplantation, and improve long-term survival for some patients with HCC. METHODS: We retrospectively reviewed the medical records of patients undergoing LDLT for HCC from November 2008 to December 2015 at a single institution in Korea. In total, 165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome the ABO blood group barrier, including pretransplant plasma exchange and rituximab administration (300-375 mg/m2 /body surface area). RESULTS: We performed 1:1 propensity score matching and included 165 patients in each group. 82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within conventional Milan criteria, respectively, and 92.1% and 92.7% of patients in each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both groups showing comparable recurrence-free survival rates (hazard ratio [HR] 1.14; 95% CI 0.68-1.90; p = 0.630) and overall patient-survival outcomes (HR 1.10; 95% CI 0.60-2.00; p = 0.763). CONCLUSIONS: These findings suggested that ABO-incompatible liver transplantation is a feasible option for patients with HCC, especially for those with compensated cirrhosis with HCC within conventional Milan criteria. LAY SUMMARY: Despite hypothetical immunological concerns that the desensitization protocol for breaking through the ABO blood group barrier might have a negative impact on the recurrence of hepatocellular carcinoma, our experience demonstrated no significant differences in the long-term overall survival and recurrence-free survival rates between patients receiving ABO-compatible or ABO-incompatible liver transplantation. In conclusion, results from our institution indicated that ABO-incompatible living-donor liver transplantation constitutes a potentially feasible option for patients with hepatocellular carcinoma, especially those with compensated cirrhosis with hepatocellular carcinoma within conventional Milan criteria.

Low Graft Attenuation at Unenhanced CT: Association with 1-Month Mortality or Graft Failure after Liver Transplantation.

Purpose To investigate whether low graft attenuation at unenhanced computed tomography (CT) is associated with 1-month mortality or graft failure after liver transplant and determine its diagnostic performance. Materials and Methods Included were 663 recipients who underwent CT imaging within 7 days after liver transplant between December 2014 and August 2016. Initial poor function (IPF) was diagnosed by using a combination of laboratory values within 7 days after liver transplant and subdivided patients into primary and secondary IPF. At 1 month after the operation, mortality and graft failure or survival in recipients was categorized. Two radiologists who were blinded to clinical data retrospectively and independently evaluated graft attenuation on unenhanced CT images (high or isoattenuation, graft attenuation greater than or equal to that of spleen; low, graft attenuation less than that of spleen). The interobserver agreement was evaluated by using intraclass correlation coefficient and κ statics. Incidence of low graft attenuation between recipients with IPF and those with normal function was compared by using χ2 test. The relationship between graft attenuation and outcome in primary and secondary IPF was evaluated by using log-rank test. Results Of 663 recipients, 114 had IPF (80 primary; 34 secondary). After 1 month, 11 had graft failure or died, whereas 652 survived. Low graft attenuation was more common in patients with IPF than in normal-function patients (P < .001). In the primary group (those without identifiable cause), 15 patients had low graft attenuation, which led to mortality or graft failure within 1 month in seven of those patients. No recipient with high or isoattenuation had 1-month mortality or graft failure (P < .001). The secondary group (those with identifiable cause) showed no significant association between graft attenuation and 1-month mortality and graft failure (P = .181). Values of low graft attenuation for 1-month mortality and graft failure in primary IPF were positive predictive value, 46.7%; negative predictive value, 100%; sensitivity, 100%; specificity, 89.0%; and accuracy, 90.0%. There was excellent interobserver agreement in the assessment of graft attenuation (intraclass correlation coefficient, 0.957; κ = 1.00). Conclusion Low graft attenuation can be associated with 1-month mortality or graft failure in liver graft recipients with primary IPF. © RSNA, 2017.

Computed tomography findings in ABO-incompatible living donor liver transplantation recipients with biliary strictures.

OBJECTIVES: To evaluate CT findings of biliary strictures in ABO-incompatible living donor liver transplantation (LDLT) recipients, with emphasis on associated 1-month post-transplantation CT findings, and evaluate clinical outcomes. METHODS: Of 351 ABO-incompatible recipients, we retrospectively evaluated CT scans in 65 recipients with biliary stricture. The biliary strictures on CT scans were classified as type A (perihilar) and type B (diffuse). Precedent CT abnormality patterns and the presence of a periportal halo sign at 1-month post-transplantation were evaluated. For each patient, clinical outcomes were evaluated. RESULTS: Of 65 ABO-incompatible recipients with biliary strictures, 36.9% had type B strictures. Compared with biliary strictures at diagnosis, similar CT abnormality patterns were observed for 84.4% in type A and 86.4% in type B strictures at 1-month post-transplantation. Complex periportal halo signs on the 1-month post-transplantation CT were more frequently noted for type B than type A strictures (86.4% vs. 3.1%, P < 0.001). Progressive clinical outcomes were more frequently observed for type B than type A strictures (79.2% vs. 26.8%, P < 0.001), with a significantly shorter graft survival time (46.4 months vs. 90.8 months, P < 0.001). CONCLUSION: CT abnormality patterns and complex periportal halo signs on 1-month post-transplantation CT may be clinically useful for managing biliary strictures in ABO-incompatible LDLT recipients. Key Points • Of ABO-incompatible LDLT recipients, type B biliary stricture incidence was 6.8%. • Of type B strictures, 86.4% exhibited similar CT abnormality patterns at 1-month post-transplantation. • Complex periportal halo at 1 month was significantly associated with type B strictures. • Progressive clinical outcomes were more frequently observed in type B strictures.

Efficacy and safety of superselective trans-catheter arterial embolization of upper and lower gastrointestinal bleeding using N-butyl-2-cyanoacrylate.

PURPOSE: To evaluate the efficacy and safety of superselective trans-catheter arterial embolization (TAE) with N-butyl-2-cyanoacrylate (NBCA) for patients with acute non-variceal upper and lower gastrointestinal (GI) bleeding. METHODS: TAE using NBCA was performed in 21 patients (13 males, 8 females, mean age 60.9 years) with acute non-variceal upper (n = 15) and lower (n = 6) GI bleeding. TAE using other embolic agents was performed in 25 patients (13 males, 12 females, mean age 69.1 years) with acute non-variceal upper (n = 16) and lower (n = 9) GI bleeding. Technical success, clinical success, clinical failure, major and minor complications, bleeding-related 30-day mortality, and overall in-hospital mortality were analyzed. RESULTS: In 21 patients who underwent TAE with NBCA, the overall technical success was 100% (21/21) and overall clinical success was 72.2% (13/18). Uncontrolled bleeding, recurrent bleeding, and clinical failure were seen in 11.1% (2/18), 16.7% (3/18), and 27.8% (5/18) of cases, respectively. The minor complication rate was 16.7% (4/21) and no major complications occurred. Three patients showed ischemic damage in the treated lesion and one patient showed epigastric pain. The bleeding-related 30-day mortality and overall in-hospital mortality rates were 16.7% (3/18) and 28.6% (6/21), respectively. Two patients died of septic shock and one died of myocardial infarction within 30 days after TAE. In 25 patients who underwent TAE with other agents, the overall technical success was 100% (25/25), and the overall clinical success was 68.2% (15/22). The rates of uncontrolled bleeding, recurrent bleeding, clinical failure, bleeding-related 30-day mortality, and overall in-hospital mortality were 0.5% (1/22), 22.7% (5/22), 31.8% (7/22), 22.7% (5/22), and 32.0% (8/25), respectively. CONCLUSIONS: TAE with NBCA for acute non-variceal upper and lower GI bleeding proved to be a technically feasible, safe, and effective treatment modality. Thus, NBCA could be used as a primary embolic agent for controlling GI bleeding.

Measurement of liver volumes by portal vein flow by Doppler ultrasound in living donor liver transplantation.

BACKGROUND: The accurate estimation of liver volume and right/left ratio in donor candidates is critical, but there is no method using portal vein (PV) flow. METHODS: Of 125 donor candidates, right/left liver volume ratio was estimated using ultrasound (US)-PV area ratio and Doppler US-PV flow ratio, and the results were compared with CT volumetry. We analyzed these results in 76 donors who underwent hemihepatectomy. We evaluated diagnostic values of Doppler US-PV flow for <30% remnant liver volume high-risk donors, and compared liver volume by Doppler US-PV flow with actual graft weight. RESULTS: In 125 donor candidates, 96.8% showed <10% difference between liver volume ratio by Doppler US-PV flow ratio and CT volumetry. Compared with CT volumetry, the mean percentage difference of liver volume ratio by Doppler US-PV flow ratio was significantly smaller than that by US-PV area ratio (±0.7% vs ±6.3%, P<.001). In 76 donors who underwent hemihepatctomy, results were similar, showing smaller mean percentage difference of liver volume ratio by Doppler US-PV flow ratio than that by US-PV area ratio (±1.0% vs ±6.0%, P<.001). Sensitivity and specificity for <30% remnant liver volume donors were 76.9% and 76.8%. Blood-free liver volume by Doppler US-PV flow was linearly correlated with graft weight (R2 =0.770, P<.001), although significantly different, with 8.5% error ratio (669.3±173.2 vs 633.7±187.1, P=.001). CONCLUSION: Doppler US-PV flow can effectively estimate right/left liver volume ratio in initial donor investigation. However, Doppler US-PV flow is not accurate in assessing donors with <30% remnant liver volume and in estimating actual graft weight.

N-butyl-2 cyanoacrylate (NBCA) embolus in the graft portal vein after portosystemic collateral embolization in liver transplantation recipient: what is the clinical significance?

Background An N-butyl-2 cyanoacrylate (NBCA) embolus in the graft portal vein was frequently observed after an intraoperative embolization of portosystemic collaterals performed to prevent portal steal in liver transplant (LT) recipients. The radiological and clinical features of NBCA emboli have not yet been described. Purpose To describe radiological and clinical features of NBCA embolus in graft portal vein after portosystemic collateral embolization in LT recipients. Material and Methods A total of 165 consecutive LT recipients who had undergone intraoperative NBCA embolization of varix were found in single institution's computerized databases of a clinical cohort of LT. Patients were evaluated for NBCA emboli (categorized into major and minor emboli according to location) on first postoperative computed tomography (CT). All electronic medical records and radiologic studies including follow-up was evaluated to determine any radiological and clinical abnormality associated with NBCA embolus. Results NBCA emboli were found in 24% (39/165) of recipients. Although most patients had minor emboli (77%, 30/39) without remarkable ultrasonography (US) abnormalities, seven (78%) of nine recipients with major emboli showed intraluminal echogenic lesions in graft portal vein on grayscale US, and five of them (71%) showed partial portal flow obstruction, although none exhibited any abnormality on contrast-enhanced US. Recipients with NBCA portal emboli showed no significant clinical abnormalities and were discharged safely. NBCA embolus eventually disappeared mostly within six months (82%, 32/39). Conclusion NBCA emboli are frequently observed after portosystemic collateral embolization in LT recipients and are not associated with poor clinical outcome. They may mimic ordinary thromboemboli on US.

Reliable transfer of multiple perforator-based pedicled flaps: Surgical technique and clinical outcomes.

PURPOSE: Although an increase in flap perfusion by incorporating multiple perforators has been demonstrated with free perforator flaps, whether the same efficacy can be achieved with pedicled flaps remains unclear, due to concerns regarding pedicle tension or kinking during flap transposition. The aim of this report was to investigate the reliability of multiple perforator-based pedicled flaps in a series of clinical cases. PATIENTS AND METHODS: Twenty-six patients undergoing soft tissue reconstruction using multiple perforator-based pedicled flaps from 2008 to 2012 were reviewed. The causes of the defects were oncologic (n = 15) or chronic wounds (n = 11). The defect sites were the trunk (n = 19), lower extremities (n = 4), head and neck (n = 2), and upper extremities (n = 1). Diverse flap types were used, including the superior gluteal artery perforator flap, the lateral femoral circumflex artery perforator flap, the medial femoral circumflex artery perforator flap, and the thoracodorsal artery perforator flap. The flaps were transposed in a rotation-and-advancement manner after skeletonizing each perforator and proximally dissecting the pedicle. The donor site was closed primarily. RESULTS: Mean flap size was 125.2 cm2 , and the mean number of perforators used was 2.3 (2-5). The mean angle of pivotal rotation for flap transposition was 132.8°. No rotation-related problems including pedicle kinking or twisting developed, and all flaps survived completely. No significant donor-site morbidity was observed. The mean follow-up period was 38.1 months. CONCLUSIONS: This report suggests that through meticulous dissection of pedicles of sufficient length, the multiple perforator-based pedicled flaps can be successfully transposed while minimizing the risk of pedicle tethering. © 2015 Wiley Periodicals, Inc. Microsurgery 37:105-111, 2017.