Mito-FUNCAT-FACS reveals cellular heterogeneity in mitochondrial translation.

Mitochondria possess their own genome that encodes components of oxidative phosphorylation (OXPHOS) complexes, and mitochondrial ribosomes within the organelle translate the mRNAs expressed from the mitochondrial genome. Given the differential OXPHOS activity observed in diverse cell types, cell growth conditions, and other circumstances, cellular heterogeneity in mitochondrial translation can be expected. Although individual protein products translated in mitochondria have been monitored, the lack of techniques that address the variation in overall mitochondrial protein synthesis in cell populations poses analytic challenges. Here, we adapted mitochondrial-specific fluorescent noncanonical amino acid tagging (FUNCAT) for use with fluorescence-activated cell sorting (FACS) and developed mito-FUNCAT-FACS. The click chemistry-compatible methionine analog L-homopropargylglycine (HPG) enabled the metabolic labeling of newly synthesized proteins. In the presence of cytosolic translation inhibitors, HPG was selectively incorporated into mitochondrial nascent proteins and conjugated to fluorophores via the click reaction (mito-FUNCAT). The application of in situ mito-FUNCAT to flow cytometry allowed us to separate changes in net mitochondrial translation activity from those of the organelle mass and detect variations in mitochondrial translation in cancer cells. Our approach provides a useful methodology for examining mitochondrial protein synthesis in individual cells.

Characterization and role of collagen gene expressing hepatic cells following partial hepatectomy in mice.

BACKGROUND AND AIMS: The mechanism underlying liver regeneration following partial hepatectomy (PH) is not fully elucidated. We aimed to characterize collagen gene expressing hepatic cells following PH and examine their contribution to liver regeneration. APPROACH AND RESULTS: Col-GFP mice, which express GFP under the control of the collagen gene promoter, were used to detect collagen gene expressing cells following PH. The GFP-expressing cells were analyzed via single-cell RNA sequencing (scRNA-seq). Additionally, Col-ER Cre/RFP and Col-ER Cre/DTA mice were utilized to examine the cell fates and functional roles of collagen gene expressing cells in liver regeneration, respectively. The number of collagen gene expressing cells was found to be increased on day 3 and subsequently decreased on day 7 following PH. ScRNA-seq analysis of sorted collagen gene expressing cells showed that the regenerating liver was characterized by three distinct hepatic stellate cell (HSC) clusters, including one representing classic myofibroblasts. The other HSC clusters included an intermediately activated HSC cluster and a proliferating HSC cluster. Of these, the latter cluster was absent in the CCl 4 -induced liver fibrosis model. Cell fate tracing analysis using Col-ER Cre/RFP mice demonstrated that the collagen gene expressing cells escaped death during regeneration and remained in an inactivated state in the liver. Further, depletion of these cells using Col-ER Cre/DTA mice resulted in impaired liver regeneration. CONCLUSIONS: Heterogeneous HSC clusters, one of which was a unique proliferating cluster, were found to appear in the liver following PH. Collagen gene expressing cells, including HSCs, were found to promote liver regeneration.

Effects of different exercise modes and intensities on cognitive performance, adult hippocampal neurogenesis, and synaptic plasticity in mice.

Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis.

High expression of autotaxin is associated with poor recurrence-free survival in cholangiocarcinoma.

BACKGROUND AND AIM: Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. METHODS: In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. RESULTS: High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence-free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki-67-positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer-associated fibroblasts, plasma cells, and biliary epithelial cells. CONCLUSIONS: Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA.

Development of irreversible pancreatic ductal change triggered by pancreatic duct stenting in chronic pancreatitis.

BACKGROUND AND AIM: Stent-induced ductal change is a complication of endoscopic pancreatic stent placement for chronic pancreatitis, potentially leading to irreversible changes that may contribute to pancreatic dysfunction. This study aimed to examine the long-term outcomes of stent-induced ductal change and evaluate factors that correlate with the development of irreversible ductal changes. METHODS: Between January 2008 and December 2022, 52/223 patients with chronic pancreatitis in whom an S-type plastic stent was successfully placed from the main papilla for duct stricture were detected with stent-induced ductal change on pancreatography at stent removal. We retrospectively investigated the clinical features of patients whose main pancreatic duct was reassessed by endoscopic pancreatography after >1 month without stent and whose residual stent-induced ductal change was irreversible. RESULTS: The patients with chronic pancreatitis with stent-induced ductal change (n = 28) (elevated change, 15; stricture change, 13) were evaluated using follow-up pancreatography. Eleven patients (39.3%) showed residual change associated with stent-induced ductal change, the degree of which was partial improvement, no change, and obstructive change in one, seven, and three patients, respectively. Stricture changes during stent removal and duration of stent placement that triggered ductal changes were significantly associated with the development of residual ductal changes. CONCLUSIONS: Irreversible stent-induced ductal change in patients with chronic pancreatitis was associated with stricture changes in the main pancreatic duct and continued plastic-stent placement. Careful evaluation of the pancreatic duct is required during plastic-stent placement. Early plastic-stent removal may result in an effective response to the development of stent-induced ductal change.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Focal pancreatic ductal change induced by 10-Fr S-type plastic stent in chronic pancreatitis.

BACKGROUND AND AIM: Stent-induced ductal change (SIDC) is a complication of endoscopic pancreatic stenting (EPS) in patients with chronic pancreatitis (CP). However, the evaluation of SIDC associated with S-type pancreatic plastic stent (PS) and large-caliber PS, such as 10 Fr, is limited. This study aimed to analyze the SIDC of the main pancreatic duct (MPD) associated with 10-Fr S-type PS in patients with CP. METHODS: Between January 2008 and December 2021, 132 patients with CP in whom a 10-Fr S-type PS had been installed by EPS were retrospectively reviewed. The SIDC incidence rate was examined, and the clinical features of patients with and without SIDC were investigated, including the outcomes for detected SIDC. RESULTS: Stent-induced ductal change during EPS was confirmed in 41 patients (31.1%) of 132 patients at a site coincident with the PS tip or distal flap in the MPD. All patients were asymptomatic during the development of SIDC. Morphological changes in the MPD were detected as elevated (75.6%) or bearing stricture changes (24.4%). A total of 90.2% of SIDC developed after the first 10-Fr PS installation. No significant differences were noted between the patients with and without SIDC. The outcomes of continued PS installment for SIDC showed persistence and secondary change. CONCLUSIONS: Stent-induced ductal change-associated 10-Fr PS installation was performed in just under one-third of the patients, indicating a substantial incidence rate and a possible development of SIDC from early stages onwards. More emphasis should be placed on SIDC as the complication.

Combined endoscopic endonasal and transcranial approach for internal carotid artery aneurysms: usefulness and safety of endonasal proximal control.

It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.

Effect of remimazolam on intraoperative neurophysiology monitoring of visual-evoked potential: a case series.

There are very few reports on the effects of benzodiazepines such as midazolam and diazepam on intraoperative visual-evoked potential (VEP), and there is no report on the effect of remimazolam at all. Five patients underwent neurosurgery using VEP monitoring for avoiding surgical injury to the optic nerve. In all cases, drug administration was based on actual body weight. General anesthesia was induced with propofol and remifentanil, and then maintained with propofol at target concentrations of 2.7-3.5 µg/ml for maintaining bispectral index (BIS) between 40 and 60. After resection of the tumor under stable VEP, we discontinued propofol immediately followed by infusion of remimazolam at 12 mg/kg/h for a few seconds, then reduced to 1 mg/kg/h. After a time, when blood levels of remimazolam appeared to be stable, VEP was monitored again and compared to controls. In all cases, we were able to confirm that there was reproducibility. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for VEP in neurosurgery.

[Assessment of Motor and Language Function during Awake Surgery].

Awake surgery enables the evaluation of neurological functions that are difficult to assess with a conventional electrophysiological examination and is useful in the evaluation of language function. Awake surgery is a team effort involving anesthesiologists and rehabilitation physicians who evaluate motor and language functions, and information sharing during the perioperative period is important. Some points regarding surgical preparation and anesthesia methods are unique and must be well understood. For example, supraglottic airway devices must be used to secure the airway, and ventilation must be checked for availability when positioning the patient. Preoperative neurological evaluation is important in determining the method of intraoperative neurological evaluation, including choosing the simplest possible method of evaluation and sharing the information with the patient prior to surgery. Motor function assessment evaluates small movements that do not affect the surgery. Visual naming and auditory comprehension are useful in the evaluation of language function.

Increased Expressions of Programmed Death Ligand 1 and Galectin 9 in Transplant Recipients Who Achieved Tolerance After Immunosuppression Withdrawal.

Programmed death 1 (PD1)/its ligand PD-L1 concomitant with T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and the forkhead box P3 (FOXP3) might be involved in tolerance after liver transplantation (LT). Liver biopsies from 38 tolerant, 19 nontolerant (including 16 samples that triggered reintroduction of immunosuppression [IS] and 19 samples after IS reintroduction), and 38 control LT patients were studied. The expressions of PD1, PD-L1, Gal-9, and FOXP3 were determined by immunohistochemical and immunofluorescence (IF) staining. The success period of IS withdrawal was calculated using Kaplan-Meier curve analysis. Tolerant and control patients exhibited higher PD-L1, Gal-9, and FOXP3 levels than nontolerant patients at the moment of triggering IS reintroduction. High expressions of PD-L1 and Gal-9 were associated with prolonged success of tolerance (83.3% versus 36.7% [P < 0.01] and 73.1% versus 42.9% [P = 0.03]). A strong correlation between PD-L1 and Gal-9 expression levels was detected (Spearman r = 0.73; P ≤ 0.001), and IF demonstrated colocalization of PD-L1 and Gal-9 in the cytoplasm of hepatocytes. In conclusion, the present study demonstrated that increased expressions of PD-L1 and Gal-9 were associated with sustained tolerance after IS withdrawal in pediatric liver transplantation.

Macrohistory of Moyamoya Disease Analyzed Using Artificial Intelligence.

INTRODUCTION: Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular networks called moyamoya vessels. The objective of this review was to provide a holistic view of the epidemiology, etiology, clinical findings, treatment, and pathogenesis of moyamoya disease. A literature search was performed in PubMed using the term "moyamoya disease," for articles published until 2021. RESULTS: Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the "clinical background" cluster were published from the 1970s. However, in the "treatment" and "genetics" clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomic, transcriptomic, and epigenetic profiling (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. Our literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression. CONCLUSION: We analyzed the content vectors in abstracts using AI, and reviewed the pathophysiology, clinical background, radiological features, treatments, and genetic peculiarity of moyamoya disease.

Validity of Preoperative Screening Before Open-Heart Surgery in Reduction of Perioperative Ischemic Stroke.

OBJECTIVES: Cerebrovascular event after open-heart surgery is a critical complication and contributes to poor prognosis, including increased mortality. The purpose of this study is to investigate the appropriate preoperative risk assessment and monitoring for reducing the risk of ischemic stroke after open-heart surgery. MATERIALS AND METHODS: 184 patients who underwent surgery for valvular heart disease were included in this study. Near-infrared oxygen saturation monitoring (INVOS system) was performed during open-heart surgery. For the purpose of perioperative stroke risk assessment, we evaluated the clinical and radiological factors of the group that underwent preoperative consultation and the group that did not, and of the patients with and without postoperative ischemic stroke. RESULTS: Preoperative consultation was performed in 60 cases. Large vessel steno-occlusive disease was found in nine cases, of which three had undergone revascularization surgery. Cerebral infarction developed in four cases, all of which had no large vessel steno-occlusive disease. There was no significant association between the development of postoperative ischemic stroke and presence of large vessel steno-occlusive disease. Preoperative baseline INVOS value was significantly low in the ischemic stroke group (49.5 ± 12.5) compared to the non-ischemic stroke group (66.8 ± 10.0), (P = 0.012). CONCLUSIONS: In open-heart surgery for valvular heart disease, low preoperative baseline INVOS values were associated with cerebral ischemic stroke after surgery. The combination of appropriate preoperative screening for large vessel steno-occlusive disease and measurement of INVOS could be used as a simple and useful method in screening for the risk of ischemic stroke after open-heart surgery.

[A case of unresectable advanced gastric cancer with oral mucosal necrosis during combination therapy with nab-paclitaxel plus ramucirumab].

A 61-year-old patient with advanced gastric cancer was treated with ramucirumab plus albumin-suspended paclitaxel as second-line treatment. The treatment resulted in exposure of the right mandible around an implant. The implant was removed, and sequestration was not observed. The patient was diagnosed with oral mucosal necrosis. Thus, implants may cause mucosal necrosis due to angiogenesis inhibitors.

Utility of Mac-2 Binding Protein Glycosylation Isomer to Evaluate Graft Status After Liver Transplantation.

Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel liver fibrosis biomarker, but there are few studies on M2BPGi in liver transplantation (LT) recipients. This study aimed to evaluate the utility of M2BPGi measurement in LT recipients. We collected the clinicopathological data of 233 patients who underwent a liver biopsy at Kyoto University Hospital after LT between August 2015 and June 2019. The median values of M2BPGi in patients with METAVIR fibrosis stages F0, F1, F2, and ≥F3 were 0.61, 0.76, 1.16, and 1.47, respectively, whereas those in patients with METAVIR necroinflammatory indexes A0, A1, and ≥A2 were 0.53, 1.145, and 2.24, respectively. Spearman rank correlation test suggested that the necroinflammatory index had a stronger correlation to the M2BPGi value than the fibrosis stage. The area under the receiver operating characteristic curve of M2BPGi to predict ≥A1 was 0.75, which was significantly higher than that of any other liver fibrosis and inflammation marker. Patients with a rejection activity index (RAI) of ≥3 had a higher M2BPGi value than those with RAI ≤ 2 (P = 0.001). Patients with hepatitis C virus viremia had a higher M2BPGi value than sustained virological responders or those with other etiologies. In conclusion, the present study demonstrated that M2BPGi values are more strongly influenced by necroinflammatory activity and revealed M2BPGi, which has been thought to be a so-called fibrosis marker, as a disease activity marker in transplant recipients. M2BPGi measurement may be useful to detect early stage liver inflammation that cannot be detected by routine blood examination of LT recipients.

Nodal-based radiomics analysis for identifying cervical lymph node metastasis at levels I and II in patients with oral squamous cell carcinoma using contrast-enhanced computed tomography.

OBJECTIVE: Discriminating metastatic from benign cervical lymph nodes (LNs) in oral squamous cell carcinoma (OSCC) patients using pretreatment computed tomography (CT) has been controversial. This study aimed to investigate whether CT-based texture analysis with machine learning can accurately identify cervical lymph node metastasis in OSCC patients. METHODS: Twenty-three patients (with 201 cervical LNs [150 benign, 51 metastatic] at levels I-V) who underwent preoperative contrast-enhanced CT and subsequent cervical neck dissection were enrolled. Histopathologically proven LNs were randomly divided into the training cohort (70%; n = 141, at levels I-V) and validation cohort (30%; n = 60, at level I/II). Twenty-five texture features and the nodal size of targeted LNs were analyzed on the CT scans. The nodal-based sensitivities, specificities, diagnostic accuracy rates, and the area under the curves (AUCs) of the receiver operating characteristic curves of combined features using a support vector machine (SVM) at levels I/II, I, and II were evaluated and compared with two radiologists and a dentist (readers). RESULTS: In the validation cohort, the AUCs (0.820 at level I/II, 0.820 at level I, and 0.930 at level II, respectively) of the radiomics approach were superior to three readers (0.798-0.816, 0.773-0.798, and 0.825-0.865, respectively). The best models were more specific at levels I/II and I and accurate at each level than each of the readers (p < .05). CONCLUSIONS: Machine learning-based analysis with contrast-enhanced CT can be used to noninvasively differentiate between benign and metastatic cervical LNs in OSCC patients. KEY POINTS: • The best algorithm in the validation cohort can noninvasively differentiate between benign and metastatic cervical LNs at levels I/II, I, and II. • The AUCs of the model at each level were superior to those of multireaders. • Significant differences in the specificities at level I/II and I and diagnostic accuracy rates at each level between the model and multireaders were found.

Novel mouse model for cholestasis-induced liver fibrosis resolution by cholecystojejunostomy.

BACKGROUND AND AIM: Studies on the resolution of liver fibrosis are becoming more important in this era of etiologic eradication. In contrast to the extensive research on the recovery of liver fibrosis induced by hepatotoxic injuries, regression of cholestatic liver fibrosis has been insufficiently examined owing to the limited availability of animal models. METHODS: We examined our novel recanalization mice model of biliary obstruction, involving anastomosis between the gallbladder and jejunum (G-J anastomosis) by invagination. Transgenic mice expressing green fluorescent protein (GFP) under the collagen 1(α)1 promoter underwent G-J anastomosis 14 days after bile duct ligation (BDL) and were sacrificed 14 days later. RESULTS: Transaminase and total bilirubin levels decreased to almost normal values on day 14 after G-J anastomosis. G-J anastomosis resulted in dramatic reversal of liver fibrosis induced by BDL. Activated portal fibroblasts (PFs) double-positive for GFP and Thy-1 on immunofluorescence in the liver of BDL-injured mice became less noticeable following G-J anastomosis. Messenger RNA expression of markers for activated PFs in the liver was downregulated after anastomosis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were induced by BDL. After anastomosis, expressions of MMP-3, 8 as well as hepatocyte growth factor were further upregulated, whereas those of TIMP-1 and TIMP-3 were markedly downregulated. CONCLUSIONS: Our established G-J anastomosis model is associated with fibrosis resolution and reduced PF activation through reopening of bile duct obstruction and will be valuable for studying the recovery process of cholestatic liver fibrosis.

Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma: A Case Controlled Study with Propensity Score Matching.

BACKGROUND: Several studies have suggested that laparoscopic liver resection (LLR) is associated with fewer postoperative complications than open liver resection (OLR) for hepatocellular carcinoma (HCC). However, this issue remains controversial since the data may have been attributable to an imbalance in patients' background. METHODS: We retrospectively analyzed 290 hepatectomies for HCC undertaken between 2011 and 2019. Liver resection difficulty was based on the 3 levels of the Institut Mutualiste Montsouris classification. Resection ratio was calculated using computed tomography volumetry. Patient characteristics were compared between the LLR and OLR groups. Propensity score matching (PSM) was adopted to adjust the imbalance between the cohorts, and the incidence of postoperative complications was compared. RESULTS: The difficulty and resection ratio were significantly lower in LLR (n = 112) than in OLR (n = 178) (difficulty grade I/II/III: 84/10/18 vs. 43/39/96, p < 0.001; resection ratio: 11.4 ± 12.7 vs. 22.7 ± 17.2%, p < 0.001). The incidence of postoperative complications (Clavien-Dindo grade III or more) was lower in LLR (2.7% vs. 21.9%, p < 0.001), which was mainly attributable to fewer incidences of ascites and pleural effusion. PSM generated 68 well-matched patients in each group. The lower incidence of postoperative complications in LLR was also maintained in the PSM cohort (2.9% vs. 16.2%, p = 0.017). On multivariate analysis, LLR was the independent predictor of postoperative complications (OR 0.184, 95% CI 0.051-0.672, p = 0.010). CONCLUSION: The present study demonstrated that a laparoscopic approach reduces the incidence of postoperative complications in liver resection for HCC.

Low level of postoperative plasma antithrombin III is associated with portal vein thrombosis after liver surgery.

PURPOSE: Although decreased antithrombin-III (AT-III) is a risk factor for portal vein thrombosis (PVT) in patients with liver cirrhosis, the association between postoperative PVT and postoperative AT-III levels is unknown in patients undergoing hepatectomy. METHODS: Patients who underwent hepatectomy between 2015 and 2018 were retrospectively analyzed. Postoperative PVT was assessed on CT at days 6-9 after hepatectomy. One-to-one propensity score (PS) matching was used to match the baseline characteristics. RESULTS: Of the 295 patients included in this analysis, 19 patients (6.4%) were diagnosed with postoperative PVT. The AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (AUC, 0.644; cut-off value, 60%; p = 0.032). Multivariate analysis revealed that AT-III levels ≤ 60% on POD3 (OR, 3.01; 95% CI 1.02-8.89; p = 0.046), cirrhosis (OR, 5.88; 95% CI 1.92-18.0; p = 0.002) and right-sided hepatectomy (OR, 4.16; 95% CI 1.45-11.9; p = 0.0079) were significant risk factors for postoperative PVT. After PS matching, 56 patients with and without AT-III supplementation were analyzed. The two groups had a similar incidence of PVT (p = 0.489). CONCLUSIONS: Patients with AT-III levels ≤ 60% on POD3 should be carefully followed up regarding postoperative PVT. Our results did not support the efficacy of routine AT-III supplementation for the prophylaxis of postoperative PVT.