Percutaneous transhepatic treatment for biliary stricture after duct-to-duct biliary anastomosis in living donor liver transplantation: a 9-year single-center experience.

OBJECTIVES: To investigate clinical outcomes of percutaneous transhepatic treatment for biliary stricture after duct-to-duct biliary anastomosis in living donor liver transplantation (LDLT). METHODS: This retrospective study examined baseline characteristics, procedural details, clinical outcomes, drainage catheter removal rate within 8 months, and recurrence after catheter removal using patients' medical records and images. Risk factors for failure of drainage catheter removal within 8 months and recurrence of biliary stricture after drainage catheter removal were assessed via univariable and multivariable analyses. RESULTS: A total of 112 patients (53.4 ± 8.79 years, 91 men) were evaluated. Multiple drainage catheters were placed in 75 patients (70.0%). Drainage catheters were successfully removed in 107 patients (95.5%). Failure of drainage catheter removal within 8 months was associated with hepatic artery complications (p = 0.034) and strictures requiring alternative passage techniques (p = 0.034). The cumulative primary patency rates after drainage catheter removal at 1, 2, 3, and 5 years were 85.4%, 79.8%, 75.8%, and 68.4%, respectively. Recurrence of biliary stricture was associated with the presence of an untreated isolated sectoral duct (aHR, 3.632; 95% CI, 1.086-12.150, p = 0.037) and with concurrent bile leaks (aHR, 2.475; 95% CI, 1.090-5.621, p = 0.031). CONCLUSION: Percutaneous transhepatic treatment was effective for the treatment of biliary strictures after duct-to-duct biliary anastomosis in LDLT. Multiple drainage catheter maintenance was needed because multiple strictures often occurred in these patients. KEY POINTS: • Percutaneous transhepatic treatments are useful and effective for the treatment of biliary stricture after duct-to-duct biliary anastomosis in living donor liver transplantation (LDLT), although an endoscopic approach is available for this type of reconstruction. • Multiple drainage catheters were frequently placed in these patients because of multiple complex strictures. • We found that recurrence after drainage catheter removal was associated with isolation of the sectoral duct and with concurrent bile leaks.

Spectral CT Imaging-Based Quantification of Iodized Oil Retention following Chemoembolization: Phantom and Animal Studies.

PURPOSE: To evaluate accuracy of iodine quantification using spectral CT and the potential of quantitative iodized oil analysis as an imaging biomarker of chemoembolization. MATERIALS AND METHODS: A phantom of an artificial liver with 6 artificial tumors containing different amounts of iodized oil (0-8 vol%) was scanned by spectral CT, and iodized oil density (mg/mL) and Hounsfield unit (HU) values were measured. In addition, VX2 hepatoma was induced in 23 rabbits. After chemoembolization using iodized oil chemoemulsion, the rabbits were scanned by spectral CT. The accumulation of iodized oil in the tumor was quantified in terms of iodized oil density and HUs, and the performances in predicting a pathologic complete response (CR) were evaluated by receiver operating characteristic curve analyses. RESULTS: The mean difference between true iodine densities and spectral image-based measurements was 0.5 mg/mL. Mean HU values were highly correlated with mean iodine density (r2 = 1.000, P < .001). In the animal study, a pathologic CR was observed in 17 of 23 rabbits (73.9%). The range of area under the curve values of iodine and HU measurements was 0.863-0.882. A tumoral iodine density of 3.57 mg/mL, which corresponds to 0.7 vol% iodized oil in the tumor, predicted a pathologic CR with a sensitivity of 70.6% and a specificity of 100.0%. CONCLUSIONS: Spectral CT imaging has a potential to predict tumor responses after chemoembolization by quantitatively assessing iodized oil in targets.

Added Value of Integrated Whole-Body PET/MRI for Evaluation of Colorectal Cancer: Comparison With Contrast-Enhanced MDCT.

OBJECTIVE: The purpose of this study was to evaluate the added clinical value of PET/MRI compared with conventional contrast-enhanced MDCT (CECT) alone in the evaluation of patients with colorectal cancer. MATERIALS AND METHODS: The study population comprised 51 patients with colorectal cancer who underwent (18)F-FDG PET/MRI and CECT within a 90-day interval between October 2012 and August 2013. Two reviewers in consensus evaluated whether PET/MRI added value to CECT for lesion detection and characterization and assessed whether changes in treatment strategies were made. The malignancy probability of each lesion was assessed on a 5-point scale. ROC analyses were performed with histopathologic findings, imaging, and clinical follow-up as the reference standards. Two reviewers evaluated the presence or absence of pulmonary metastatic nodules on PET/MR images that had been detected on chest CT scans. RESULTS: PET/MRI added value to CECT for 14 of 51 patients (27.5%) in terms of better characterization (12/51 [23.5%]) and additional detection (2/51 [3.9%]) of extracolonic lesions. The additional information from PET/MRI led to a change in treatment strategy for 11 of 51 (21.6%) patients. ROC analyses showed that PET/MRI was significantly superior to CT in depicting colorectal cancer (p < 0.05). The rate of detection of pulmonary metastatic nodules with PET/MRI was 52.9% (9/17). CONCLUSION: Integrated whole-body PET/MRI added value to CECT in the detection of metastatic lesions and characterization of indeterminate lesions, albeit with limited performance for small pulmonary metastatic nodules. The results suggest that PET/MRI may aid in the selection of more appropriate treatment strategies for patients with colorectal cancer.

Transarterial chemoembolization with additional cisplatin infusion for hepatocellular carcinoma invading the hepatic vein.

PURPOSE: To evaluate retrospectively the efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC) with hepatic vein invasion by comparing the results of conventional transarterial chemoembolization and modified transarterial chemoembolization. MATERIALS AND METHODS: From January 2000 to December 2009, 107 patients with HCC and hepatic vein invasion and Child-Pugh class A were treated by transarterial chemoembolization. Modified transarterial chemoembolization (conventional transarterial chemoembolization followed by additional infusion of 50-100 mg of cisplatin) has been undertaken since 2005. Clinical and radiologic data were reviewed and analyzed retrospectively. The overall survival rates were obtained by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Conventional transarterial chemoembolization was performed in 60 patients, and modified transarterial chemoembolization was performed in 47 patients. No significant differences were observed in major complications between the groups. The median survival was longer in the modified group compared with the conventional group (9.7 mo, 95% confidence interval [CI], 4.3-15.1, vs 6.7 mo, 95% CI, 4.8-8.5; P = .047). By subgroup analysis, modified transarterial chemoembolization increased survival of patients with a diffuse tumor type (8.9 mo, 95% CI, 5.9-11.9, vs 3.8 mo, 95% CI, 2.5-5.0; P = .000) and patients without metastasis (20.9 mo, 95% CI, 12.2-29.5, vs 7.3 mo, 95% CI, 4.1-10.5; P = .005). Multivariate analysis identified three independent predictive factors for mortality: diffuse tumor type (P = .001), metastasis (P = .009), and modified transarterial chemoembolization protocol (P = .003). CONCLUSIONS: A survival benefit was suggested with transarterial chemoembolization with additional cisplatin infusion over conventional transarterial chemoembolization in patients with HCC invading the hepatic vein.

Extraluminal Recanalization for Biliary Duct-to-Duct Anastomotic Obstruction After Living Donor Liver Transplantation: Experience in Eight Patients.

PURPOSE: To investigate clinical outcomes and safety of extraluminal recanalization for duct-to-duct anastomotic obstruction after living donor liver transplantation (LDLT). MATERIALS AND METHODS: Extraluminal recanalization was performed as a salvage procedure after failure of intraluminal cannulation in eight patients who underwent percutaneous transhepatic treatment of duct-to-duct anastomotic obstruction 11.0 ± 5.27 months after LDLT between October 2012 and April 2019. Technical details, safety, and outcomes of extraluminal recanalization were investigated. RESULTS: Total ten sessions of extraluminal recanalization were performed in the eight patients with the stiff backend of a 0.035 inch hydrophilic guide wire, 22-gauge Chiba needle, or Colapinto needle. Percutaneous common bile duct access was performed in three sessions to obtain a straight course for the puncture. There was one instance of subcapsular and intraparenchymal hematoma requiring placement of an additional drainage catheter and conservative treatment. During a follow-up period ranging from 18.4 to 100.7 months, the drainage catheter was removed in seven of the eight patients, including three patients who had recurrent stricture requiring repeat percutaneous treatment and one who underwent a routine change of an endoscopic retrograde biliary drainage catheter. CONCLUSIONS: Extraluminal recanalization can be an effective and safe salvage procedure after failed intraluminal cannulation of duct-to-duct anastomotic obstruction in LDLT.

Lysine demethylase 3a in craniofacial and neural development during Xenopus embryogenesis.

Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono­ and di­methylated ninth lysine of histone 3 and belongs to the Jumonji domain­containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor­mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small­sized eyes and abnormal pigmentation. Whole­mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.

Peroxiredoxin5 Controls Vertebrate Ciliogenesis by Modulating Mitochondrial Reactive Oxygen Species.

AIMS: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development. RESULTS: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development. Depletion of Prdx5 increased levels of cellular reactive oxygen species (ROS), consequently leading to mitochondrial dysfunction and abnormal cilia formation. Proteomic and transcriptomic approaches revealed that excessive ROS accumulation on Prdx5 depletion subsequently reduced the expression level of pyruvate kinase (PK), a key metabolic enzyme in energy production. We further confirmed that the promotor activity of PK was significantly reduced on Prdx5 depletion and that the reduction in PK expression and its promoter activity led to ciliary defects observed in Prdx5-depleted cells. INNOVATION: Our data revealed the novel relationship between ROS and Prdx5 and the consequent effects of this interaction on vertebrate ciliogenesis. The normal process of ciliogenesis is interrupted by the Prdx5 depletion, resulting in excessive ROS levels and suggesting cilia as vulnerable targets of ROS. CONCLUSION: Prdx5 plays protective roles in mitochondria and is critical for normal cilia development by regulating the levels of ROS. The loss of Prdx5 is associated with excessive production of ROS, resulting in mitochondrial dysfunction and aberrant ciliogenesis.

Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development.

BACKGROUND: Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer. However, the developmental significance of KDM5C has not been explored yet. In the present study, we investigated the physiological roles of KDM5C during Xenopus laevis embryonic development. RESULTS: Loss-of-function analysis using kdm5c antisense morpholino oligonucleotides indicated that kdm5c knockdown led to small-sized heads, reduced cartilage size, and malformed eyes (i.e., small-sized and deformed eyes). Molecular analyses of KDM5C functional roles using whole-mount in situ hybridization, ß-galactosidase staining, and reverse transcription-polymerase chain reaction revealed that loss of kdm5c resulted in reduced expression levels of neural crest specifiers and genes involved in eye development. Furthermore, transcriptome analysis indicated the significance of KDM5C in morphogenesis and organogenesis. CONCLUSION: Our findings indicated that KDM5C is associated with embryonic development and provided additional information regarding the complex and dynamic gene network that regulates neural crest formation and eye development. This study emphasizes the functional significance of KDM5C in Xenopus embryogenesis; however, further analysis is needed to explore the interactions of KDM5C with specific developmental genes.

Peroxiredoxin1, a novel regulator of pronephros development, influences retinoic acid and Wnt signaling by controlling ROS levels.

Peroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of H2O2 and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers. In this study, we investigated the role of Prdx1 in pronephros development during embryogenesis. Prdx1 knockdown markedly inhibited proximal tubule formation in the pronephros and significantly increased the cellular levels of reactive oxygen species (ROS), which impaired primary cilia formation. Additionally, treatment with ROS (H2O2) severely disrupted proximal tubule formation, whereas Prdx1 overexpression reversed the ROS-mediated inhibition in proximal tubule formation. Epistatic analysis revealed that Prdx1 has a crucial role in retinoic acid and Wnt signaling pathways during pronephrogenesis. In conclusion, Prdx1 facilitates proximal tubule formation during pronephrogenesis by regulating ROS levels.

The Safety and Clinical Outcomes of Chemoembolization in Child-Pugh Class C Patients with Hepatocellular Carcinomas.

OBJECTIVE: To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC). MATERIALS AND METHODS: The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. RESULTS: Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months). CONCLUSION: Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.

The origin of the cystic artery supplying hepatocellular carcinoma on digital subtraction angiography in 311 patients.

PURPOSE: This study was designed to investigate the prevalence and patterns of origin of the cystic artery using selective angiography images obtained during chemoembolization. METHODS: Between March 2007 and January 2012, 326 patients with hepatocellular carcinoma supplied by the cystic artery were treated by chemoembolization through the cystic artery. Fifteen patients were excluded due to the difficulty in determining the origin of their cystic arteries. Thus, a total of 311 patients were included in this study. Digital subtraction angiography images were reviewed retrospectively by consensus. RESULTS: A total of 112 (36 %) patients had a total of 121 variant hepatic arteries. Double cystic arteries were present in 46 (14.8 %) patients, and total 357 cystic arteries were observed. The origin sites of the cystic artery were the following: the right hepatic artery (n = 248), the anterior sectional artery (n = 44), the segment IV artery (n = 21), the posterior sectional artery (n = 10), the left hepatic artery (n = 8), the proper hepatic artery (n = 8), the gastroduodenal artery (n = 4), and others (n = 14). In total, 103 (33 %) patients had at least one cystic artery arising from arteries other than the right hepatic artery. In patients with right hepatic artery variations, the cystic artery more frequently originated from arteries other than the right hepatic artery (p = 0.003). CONCLUSIONS: The most and second most common origins of the cystic artery are the right hepatic artery and the anterior sectional artery. In addition, the origin site of the cystic arteries is influenced by variations of hepatic arteries.

Safety of chemotherapeutic infusion or chemoembolization for hepatocellular carcinoma supplied exclusively by the cystic artery.

PURPOSE: This study was designed to evaluate the safety of chemotherapeutic infusion or chemoembolization by way of the cystic artery in patients with hepatocellular carcinoma (HCC) supplied exclusively by the cystic artery. METHODS: Between Jan 2002 and Dec 2011, we performed chemotherapeutic infusion or chemoembolization using iodized oil for the treatment of 27 patients with HCC supplied exclusively by the cystic artery. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus. RESULTS: The cystic artery originated from the main right hepatic artery in 24 (89 %) patients, from the right anterior hepatic artery in 2 (7 %) patients, and from the left hepatic artery in 1 (4 %) patient. Selective catheterization of the cystic artery was achieved in all patients. Superselection of tumor-feeding vessels from the cystic artery was achieved in 7 patients (26 %). Chemotherapeutic infusion was performed in 18 patients (67 %), and chemoembolization was performed in 9 patients (33 %). There were no major complications and only 2 minor complications, including vasovagal syncope and nausea with vomiting. Individual tumor response supplied exclusively by the cystic artery at the follow-up enhanced CT scan were complete response (n = 16), partial response (n = 3), and stable disease (n = 8). CONCLUSION: HCC supplied exclusively by the cystic artery can be safely treated without severe complications by chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.