Spin-orbit-splitting-driven nonlinear Hall effect in NbIrTe4.

The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Case report: Development of central precocious puberty in a girl with late-diagnosed simple virilizing congenital adrenal hyperplasia complicated with Williams syndrome.

Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.

Heliorhodopsin-mediated light-modulation of ABC transporter.

Heliorhodopsins (HeRs) have been hypothesized to have widespread functions. Recently, the functions for few HeRs have been revealed; however, the hypothetical functions remain largely unknown. Herein, we investigate light-modulation of heterodimeric multidrug resistance ATP-binding cassette transporters (OmrDE) mediated by Omithinimicrobium cerasi HeR. In this study, we classifiy genes flanking the HeR-encoding genes and identify highly conservative residues for protein-protein interactions. Our results reveal that the interaction between OcHeR and OmrDE shows positive cooperatively sequential binding through thermodynamic parameters. Moreover, light-induced OcHeR upregulates OmrDE drug transportation. Hence, the binding may be crucial to drug resistance in O. cerasi as it survives in a drug-containing habitat. Overall, we unveil a function of HeR as regulatory rhodopsin for multidrug resistance. Our findings suggest potential applications in optogenetic technology.

The role of glial and neuronal Eph/ephrin signaling in Drosophila mushroom body development and sleep and circadian behavior.

The Eph receptor, a prototypically large receptor protein tyrosine kinase, interacts with ephrin ligands, forming a bidirectional signaling system that impacts diverse brain functions. Eph receptors and ephrins mediate forward and reverse signaling, affecting neurogenesis, axon guidance, and synaptic signaling. While mammalian studies have emphasized their roles in neurogenesis and synaptic plasticity, the Drosophila counterparts are less studied, especially in glial cells, despite structural similarities. Using RNAi to modulate Eph/ephrin expression in Drosophila neurons and glia, we studied their roles in brain development and sleep and circadian behavior. Knockdown of neuronal ephrin disrupted mushroom body development, while glial knockdown had minimal impact. Surprisingly, disrupting ephrin in neurons or glial cells altered sleep and circadian rhythms, indicating a direct involvement in these behaviors independent from developmental effects. Further analysis revealed distinct sleep phenotypes between neuronal and glial knockdowns, underscoring the intricate interplay within the neural circuits that govern behavior. Glia-specific knockdowns showed altered sleep patterns and reduced circadian rhythmicity, suggesting an intricate role of glia in sleep regulation. Our findings challenge simplistic models of Eph/ephrin signaling limited to neuron-glia communication and emphasize the complexity of the regulatory networks modulating behavior. Future investigations targeting specific glial subtypes will enhance our understanding of Eph/ephrin signaling's role in sleep regulation across species.

MLL4 binds TET3.

Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger of MLL4 (MLL4PHD6) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4PHD6 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site of MLL4PHD6, and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3PHD7). Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.

Chemokine expression in sera of patients with microscopic polyangiitis and granulomatosis with polyangiitis.

We evaluated chemokine expression and its correlation with disease activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) (MPA/GPA). Serum CCL2, CCL4, CCL19, CXCL1, CXCL2, and CX3CL1 level in 80 patients were analysed using multiple enzyme-linked immunosorbent assays. Correlations between variables were investigated using Pearson's correlation analysis, and receiver operator curve analysis was performed to identify optimal CX3CL1 values in determining active disease. Multivariate logistic regression analysis was done to evaluate predictors of active disease. CCL4 (r = 0.251, p = 0.025), CXCL1 (r = 0.270, p = 0.015), and CX3CL1 (r = 0.295, p = 0.008) significantly correlated with BVAS, while CX3CL1 was associated with five-factor score (r = - 0.290, p = 0.009). Correlations were revealed between CCL2 and CCL4 (r = 0.267, p = 0.017), CCL4 and CXCL1 (r = 0.368, p < 0.001), CCL4 and CXCL2 (r = 0.436, p < 0.001), and CXCL1 and CXCL2 (r = 0.518, p < 0.001). Multivariate analysis revealed serum CX3CL1 levels > 2408.92 pg/mL could predict active disease (odds ratio, 27.401, p < 0.001). Serum chemokine levels of CCL4, CXCL1, and CX3CL1 showed association with disease activity and especially, CX3CL1 > 2408.92 pg/mL showed potential in predicting active MPA/GPA.

Controlling structure and interfacial interaction of monolayer TaSe2 on bilayer graphene.

Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties.

Identification of a novel splice variant in SEC23B gene in a patient with concomitant presence of congenital dyserythropoietic anemia II and Gilbert's syndrome.

BACKGROUND: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.

Selective internal limiting membrane peeling for prevention of secondary epiretinal membrane after vitrectomy for rhegmatogenous retinal detachment.

PURPOSE: We introduce selective internal limiting membrane (ILM) peeling, a guideline procedure to determine whether to remove the ILM during vitrectomy for rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective case series METHODS: Patients who underwent pars plana vitrectomy for RRD and were followed up for 12 months or longer were included. When vitreous cortex remnants (VCRs) were detected with triamcinolone acetonide, the ILM was removed; otherwise, the ILM was preserved ("selective ILM peeling"). The factors associated with the presence of VCRs and incidence of secondary epiretinal membrane (ERM) were analyzed. RESULTS: VCRs were detected in 87 of 133 eyes (65.4%) in which the ILM was removed. Younger age, better preoperative visual acuity, and vitreous hemorrhage were negatively correlated with the presence of VCRs. No ERM occurred in the eyes after ILM peeling. Among the eyes with ILM preservation, subclinical ERM was noticed in 4 eyes (8.7%), and 1 eye (2.1%) required additional surgery owing to ERM. ERM occurred more commonly in eyes with the ILM preserved (P = .004). However, no differences in the rate of additional surgeries were found between the 2 groups. CONCLUSION: Selective ILM peeling offers an alternative option to reduce the burden of ILM peeling or additional surgery.

Metabolic dysfunction-associated steatotic liver disease and risk of esophageal cancer in patients with diabetes mellitus: a nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

Concurrent Optimizations of Efficacy and Blood-Brain Barrier Permeability in New Macrocyclic LRRK2 Inhibitors for Potential Parkinson's Disease Therapeutics.

The elevated activity of leucine-rich repeat kinase 2 (LRRK2) is implicated in the pathogenesis of Parkinson's disease (PD). The quest for effective LRRK2 inhibitors has been impeded by the formidable challenge of crossing the blood-brain barrier (BBB). We leveraged structure-based de novo design and developed robust three-dimensional quantitative structure-activity relationship (3D-QSAR) models to predict BBB permeability, enhancing the likelihood of the inhibitor's brain accessibility. Our strategy involved the synthesis of macrocyclic molecules by linking the two terminal nitrogen atoms of HG-10-102-01 with an alkyl chain ranging from 2 to 4 units, laying the groundwork for innovative LRRK2 inhibitor designs. Through meticulous computational and synthetic optimization of both biochemical efficacy and BBB permeability, 9 out of 14 synthesized candidates demonstrated potent low-nanomolar inhibition and significant BBB penetration. Further assessments of in vitro and in vivo effectiveness, coupled with pharmacological profiling, highlighted 8 as the promising new lead compound for PD therapeutics.

Essential elements of physical fitness analysis in male adolescent athletes using machine learning.

Physical fitness (PF) includes various factors that significantly impacts athletic performance. Analyzing PF is critical in developing customized training methods for athletes based on the sports in which they compete. Previous approaches to analyzing PF have relied on statistical or machine learning algorithms that focus on predicting athlete injury or performance. In this study, six machine learning algorithms were used to analyze the PF of 1,489 male adolescent athletes across five sports, including track & field, football, baseball, swimming, and badminton. Furthermore, the machine learning models were utilized to analyze the essential elements of PF using feature importance of XGBoost, and SHAP values. As a result, XGBoost represents the highest performance, with an average accuracy of 90.14, an area under the curve of 0.86, and F1-score of 0.87, demonstrating the similarity between the sports. Feature importance of XGBoost, and SHAP value provided a quantitative assessment of the relative importance of PF in sports by comparing two sports within each of the five sports. This analysis is expected to be useful in analyzing the essential PF elements of athletes in various sports and recommending personalized exercise methods accordingly.

Efficacy of inverted inner limiting membrane flap technique for macular holes of ≤400 µm: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of inverted internal limiting membrane (ILM) flap technique in full-thickness macular holes (MHs) with a size of ≤400 µm compared to the ILM peeling technique. METHODS: Related literatures that compared inverted ILM flap and ILM peeling in MHs ≤ 400 µm were reviewed by searching electronic databases including Pubmed, EMbase, ClinicalTrials.gov, and Cochrane Library up to April 2023. The primary outcome measure was hole closure rate, and the secondary outcome measures were the mean postoperative best-corrected visual acuity (BCVA), retinal sensitivity, and outer status of the retinal layers, including the external limiting membrane and ellipsoid zone. The quality of the articles was assessed according to the revised version of the Cochrane risk-of-bias tool for randomized trials or the Newcastle-Ottawa scale. In the case of heterogeneity, a sensitivity analysis was conducted, and publication bias was visually evaluated using a funnel plot. RESULTS: This review included six studies with 610 eyes for the primary outcome and 385 eyes for the secondary outcomes, which were two randomized control trials and four retrospective studies. Pooled data revealed that the overall MH closure rate was 99.4% in the inverted ILM flap group and 96.2% in the ILM peeling group, without significant difference between the two groups (odds ratio = 3.91; 95% confidence interval, 0.82~18.69; P = 0.09). The inverted ILM flap technique did not have a favorable effect on the BCVA, retinal sensitivity, or recovery of the outer retinal layers. These results were consistent with those of the subgroup analysis of the different follow-up periods. No significant publication bias was observed. CONCLUSION: In eyes with MHs of ≤400 µm, both techniques demonstrated excellent surgical outcomes without significant differences. Therefore, surgical techniques can be selected according to surgeon preferences.

Torsion and clinical features in patients with acquired fourth cranial nerve palsy.

This retrospective study aimed to compare objective/subjective torsion and other clinical characteristics of patients with acquired trochlear nerve palsy. This study included 82 consecutive patients who were diagnosed with acquired fourth cranial nerve palsy between 2014 and 2021 and who were followed up for ≥ 6 months. The etiologies, ocular deviation, objective and subjective torsions were reviewed. The etiologies were classified as ischemic, traumatic, brain lesion, idiopathic, or other. The patients were classified into two groups according to the recovery state: full recovery and partial/no-recovery. We compared the torsion and clinical features based on the etiology and recovery state. The average age was 59.1 ± 11.1 years, and 58 (71.0%) of the patients were male. The most common cause was ischemic (n = 49, 59.7%) and other common causes included traumatic (n = 16, 19.5%), brain lesion (n = 8, 9.8%), idiopathic (n = 5, 6.1%) and others (n = 4, 4.9%). Of the 82 patients, 56 (68.3%) were assigned to the full recovery group, and 26 (31.7%) were assigned to the partial/no-recovery group. The average age and number of patients with ischemic causes of palsy were greater in the full recovery group (p = 0.026 and p < 0.000, respectively). The vertical deviation angle, tilted angle on the Lancaster red-green test (LRGT), proportion of patients who experienced subjective torsion on the LRGT, and head tilt were smaller in the full recovery group (p = 0.037, 0.042, 0.045, and 0.006, respectively). Ischemic trochlear nerve palsy, advanced age, a small deviation angle at the primary position, and few cases of excyclotorsion on LRGT were characteristic of the full recovery group of acquired unilateral trochlear nerve palsy patients.

Regeneration of Rabbit Calvarial Defects with Combination of Stem Cells and Enamel Matrix Derivative: A Microcomputed Tomography and Histological Evaluation Comparing Two- and Three-Dimensional Cell Constructs.

Background and Objectives: This study addresses the challenge of bone regeneration in calvarial defects, exploring the efficacy of stem cell-based therapies and enamel matrix derivative (EMD) in tissue engineering. It assesses the regenerative potential of two- and three-dimensional cell constructs combined with mesenchymal stem cells (MSCs) and EMD in rabbit calvarial defects. Materials and Methods: This research involved the use of bone-marrow-derived MSCs cultured in silicon elastomer-based concave microwells to form spheroids. White rabbits were grouped for different treatments, with Group 1 as control, Group 2 receiving only EMD, Group 3 getting EMD plus stem cells, and Group 4 being treated with EMD plus stem cell spheroids. Computed tomography (CT) and microcomputed tomography (micro-CT) imaging were used for structural assessment, while histological evaluations were conducted using hematoxylin and eosin, Masson's trichrome, and Picro-sirius red staining. Results: CT and micro-CT analyses revealed varying degrees of bone regeneration among the groups. Group 4, treated with three-dimensional MSC spheroids and EMD, showed the most significant improvement in bone regeneration. Histological analyses corroborated these findings, with Group 4 displaying enhanced bone formation and better collagen fiber organization. Conclusions: The study supported the biocompatibility and potential efficacy of three-dimensional MSC constructs combined with EMD in bone regeneration. Further investigations are needed to confirm these findings and optimize treatment protocols.

Strategies to deal with genetic analyzer-specific DNA methylation measurements.

Targeted bisulfite sequencing using single-base extension (SBE) can be used to measure DNA methylation via capillary electrophoresis on genetic analyzers in forensic labs. Several accurate age prediction models have been reported using this method. However, using different genetic analyzers with different software settings can generate different methylation values, leading to significant errors in age prediction. To address this issue, the study proposes and compares four methods as follows: (1) adjusting methylation values using numerous actual body fluid DNA samples, (2) adjusting methylation values using control DNAs with varying methylation ratios, (3) constructing new age prediction models for each genetic analyzer type, and (4) constructing new age prediction models that could be applied to all types of genetic analyzers. To test the methods for adjusting values using actual body fluid DNA samples, previously reported adjusting equations were used for blood/saliva DNA age prediction markers (ELOVL2, FHL2, KLF14, MIR29B2CHG/C1orf132, and TRIM59). New equations were generated for semen DNA age prediction markers (TTC7B, LOC401324/cg12837463, and LOC729960/NOX4) by drawing polynomial regression lines between the results of the three types of genetic analyzers (3130, 3500, and SeqStudio). The same method was applied to obtain adjustment equations using 11 control DNA samples. To develop new age prediction models for each genetic analyzer type, linear regression analysis was conducted using DNA methylation data from 150 blood, 150 saliva, and 62 semen samples. For the genetic analyzer-independent models, control DNAs were used to formulate equations for calibrating the bias of the data from each genetic analyzer, and linear regression analysis was performed using calibrated body fluid DNA data. In the comparison results, the genetic analyzer-specific models showed the highest accuracy. However, genetic analyzer-independent models through bias adjustment also provided accurate age prediction results, suggesting its use as an alternative in situations with multiple constraints.

Toxoplasma gondii IST suppresses inflammatory and apoptotic responses by inhibiting STAT1-mediated signaling in IFN-γ/TNF-α-stimulated hepatocytes.

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

Laparoscopic liver resection as a treatment option for intrahepatic cholangiocarcinoma.

Laparoscopic liver resection (LLR) remains controversial in the treatment of intrahepatic cholangiocarcinoma (ICC). The aim of the present study is to investigate the outcomes of LLR for ICC compared to open liver resection (OLR). We retrospectively reviewed patients who underwent surgery for ICC between January 2013 and February 2020. OLR and LLR were compared after propensity score matching (PSM). Overall survival (OS) and recurrence-free survival (RFS) were compared between the matched groups. During the study period, 219 patients met the inclusion criteria (OLR = 170 patients, 77.6%; LLR = 49 patients, 22.4%). Two groups of 43 patients each were analyzed after PSM. The 5-year RFS and OS were 44.6% and 47.9% in the OLR group and 50.9% and 39.8% in the LLR group, respectively. Hospital stay and intensive care unit care were significantly shorter and lower in the LLR group than in the OLR group, respectively. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the OLR group and the LLR group. Multiple tumors and lymph node metastases were predisposing factors for tumor recurrence and death in multivariate analysis. The present study suggests that LLR should be considered in selective ICC because of short hospitalization and similar oncologic outcome and overall survival.