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Abstract This study aimed to address the diagnostic challenges in distinguishing between alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized whole-slide imaging technology to conduct a comprehensive digital analysis of liver specimens collected from patients undergoing transplantation. This study included 36 and 17 patients with ALD and MASLD cirrhosis, respectively, who underwent transplantation at our institution. Digital slides were analyzed for fibrosis patterns using FibroNest™. Patient background characteristics were comparable between ALD (n = 36) and MASLD (n = 17) groups, except for sex. The ALD group exhibited thicker collagen per strand, longer and more flexural fibrosis, and a more heterogeneous distribution than the MASLD group. In patients with ALD and concomitant metabolic dysfunction, fiber distribution became relatively uniform, resembling MASLD. Application of the phenotypic fibrosis composite score achieved 100% sensitivity and specificity for ALD/MASLD diagnosis. Digital pathological analysis of the fibrosis patterns showed morphological differences between ALD and MASLD. This approach holds promise for histological differentiation, providing valuable insights beyond the current definitions based solely on alcohol intake. This study emphasizes the potential of digital pathology in refining the diagnostic criteria for hepatic disorders.

Abstract The liver requires careful handling intra‐operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like “robotic surgery in liver transplantation,” “robotic hepatectomy for hilar cholangiocarcinoma,” “robotic vascular reconstruction following hepatectomy,” “robotic repeat hepatectomy,” and “prospective trials in robotic hepatectomy.” To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5‐year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting‐edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research.

Abstract Background Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine. Methods In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs). hCLiPs were induced in mature cryo-hepatocytes using a small-molecule cocktail of TGF-β inhibitor (A-83-01, A), GSK3 inhibitor (CHIR99021, C), and 10% FBS (FAC). HBOs were then formed by seeding hCLiPs into ultralow attachment plates and culturing them with a combination of small molecules of Rock-inhibitor (Y-27632) and AC (YAC). Results These HBOs exhibited bile canaliculi of MHs connected to BD structures, mimicking bile secretion and transportation functions of the liver. The organoids showed gene expression patterns consistent with both MHs and BD structures, and functional assays confirmed their ability to transport the bile analogs of rhodamine-123 and CLF. Functional patient-specific HBOs were also successfully created from hCLiPs sourced from cirrhotic liver tissues. Conclusions This study demonstrated the potential of human HBOs as an efficient model for studying hepatobiliary diseases, drug discovery, and personalized medicine.

Aluminum alloys used in monolithic parts for aerospace applications are subjected to distortion and residual stress (RS) generated by milling, affecting the product fatigue life. Particularly, the change in RS with depth (z) has a characteristic distribution with a maximum compressive RS at a z several tens of micrometers from the surface; however, the RS value depends on the measurement method used. In this study, the RS distribution with z from the surface after milling was measured for the AA7050-T7451 aluminum alloy by two-dimensional X-ray diffraction (2D method). The results were compared with those of four prior measurement methods, and the validity of 2D method was verified. The changes in subsurface RS with z showed similar distributions under all measurement conditions except when cos(α)-XRD was employed. The 2D method provides high repeatability. The in-plane RS distribution was also measured using 2D method to investigate the effect of milling conditions on this distribution. The RS values varied markedly depending on the measurement position, particularly at a small collimator diameter of 0.146 mm, allowing detection of localized extreme RS values. The maximum RS at z = 0 mm was − 85.6 MPa at a cutting speed of vc = 200 m/s and feed per tooth of fz = 0.05 mm, while it was − 16 MPa for vc = 450 m/s and 6.8 MPa for fz = 0.2 mm, revealing that the compressive RS changes to tensile RS as vc and fz increase.

Background. Patients undergoing liver transplantation are in a state of coagulopathy before surgery because of liver failure. Intraoperative hemorrhage, massive transfusions, and post–reperfusion syndrome further contribute to coagulopathy, acidosis, and hypothermia. In such situations, temporary cessation of surgery with open abdominal management and resuscitation in the intensive care unit (ICU), which is commonly used as a damage control strategy in trauma care, may be effective. We assessed the outcomes of open abdominal management in liver transplantation and the corresponding complication rates. Methods. We retrospectively reviewed the outcomes of patients undergoing open abdominal management among 250 consecutive liver transplantation cases performed at our institution from 2009 to 2022. Results. Open abdominal management was indicated in 16 patients. The open abdomen management group had higher Model for End-stage Liver Disease scores (24 versus 16, P

Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders. The human hepatobiliary organoids (HBOs) regenerated from chemically induced liver progenitor cells converted by mature hepatocytes and the bile duct provides a bioengineering model for liver disease and hepatic metabolism. Approach & Results: Exposure of HBOs to PS-MPs with a diameter of 1 µm for 48 h causes hepatotoxicity, hepatocyte damage, and changes in bile acid metabolism. PS-MPs could be accumulated into the bile ducts of HBOs, which can be promoted by ursodeoxycholic acid, increasing bile flow and volume by activating the bile transporter of BSEP in a dose-dependent manner along with MRP-2. The accumulation of PS-MPs in the bile duct was able to be inhibited by the bile transporter inhibitor of troglitazone that could inhibit the transporters of BSEP and MRP-2, which increased the hepatotoxicity caused by PS-MPs. Conclusions: This study provides insights into the metabolic pathways of PS-MPs in the liver and suggests potential therapeutic strategies to reduce MP-induced liver damage.

Abstract Background Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. Case report The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. Conclusions To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Over the years, persistent investigations have been conducted in search of unique properties in the field of materials. In titanium alloys, this relentless pursuit is no exception, especially when aiming to combine often antagonistic characteristics such as ductility and high mechanical strength. Intending to achieve properties rarely obtainable through other processing methods, a new class of titanium alloys called HYbrid Titanium Alloys (HYTA) emerges. The primary objective of this study is to create a HYTA that harmonizes the ductility observed in Ti–42Nb with the characteristic mechanical strength of Ti-5553. To achieve this feat, the technique of Additive Manufacturing by Laser Powder Bed Fusion (AM by LPBF) was chosen to produce an alloy with 20 in wt. of Ti-5553. Additionally, considering the costs associated with powders for LBPF, the effect of incorporating recycled powders in the process was investigated. In this context, the effects of processing these powders were evaluated, analyzing the influence of morphology and oxygen content on the resulting samples. In this way, in addition to contributing to an in-depth understanding of Hybrid Titanium Alloys, it was possible to seek the optimization of costs associated with the AM technique. As a result, an alloy with unique properties was obtained with an ultimate tensile strength of 725 MPa and 24 % elongation in the as-built condition.

Abstract Background Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. Methods The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5–6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. Discussion This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. Trial registration This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

Abstract Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.

Aminophospholipids (aPL) such as phosphatidylserine are essential for supporting the activity of coagulation factors, circulating platelets, and blood cells. Phosphatidylthreonine (PT) is an aminophospholipid previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles, and isolated leukocytes from healthy volunteers using liquid chromatography–tandem mass spectrometry. The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of phosphatidylserine. PT nanodiscs strongly bound FVa and lactadherin (nM affinity) but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and extracellular vesicle from patients with coronary artery disease than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid subclass, that contributes to the procoagulant membrane, and may support thrombosis in patients at elevated risk.

Hydrodynamic cavitation is useful in many processing applications, for example, in chemical reactors, water treatment and biochemical engineering. An important type of hydrodynamic cavitation that occurs in a Venturi tube is vortex cavitation known to cause luminescence whose intensity is closely related to the size and number of cavitation events. However, the mechanistic origins of bubbles constituting vortex cavitation remains unclear, although it has been concluded that the pressure fields generated by the cavitation collapse strongly depends on the bubble geometry. The common view is that vortex cavitation consists of numerous small spherical bubbles. In the present paper, aspects of vortex cavitation arising in a Venturi tube were visualized using high-speed X-ray imaging at SPring-8 and European XFEL. It was discovered that vortex cavitation in a Venturi tube consisted of angulated rather than spherical bubbles. The tangential velocity of the surface of vortex cavitation was assessed considering the Rankine vortex model.

As the fatigue strength of metallic components may be affected by residual stress variation at small length scales, an evaluation method for studying residual stress at sub-mm scale is needed. The sin2ψ method using X-ray diffraction (XRD) is a common method to measure residual stress. However, this method has a lower limit on length scale. In the present study, a method using at a 2D XRD detector with ω-oscillation is proposed, and the measured residual stress obtained by the 2D method is compared to results obtained from the sin2ψ method and the slitting method. The results show that the 2D method can evaluate residual stress in areas with a diameter of 0.2 mm or less in a stainless steel with average grain size of 7 μm. The 2D method was further applied to assess residual stress in the stainless steel after treatment by laser cavitation peening (LCP). The diameter of the laser spot used for LCP was about 0.5 mm, and the stainless steel was treated with evenly spaced laser spots at 4 pulses/mm2. The 2D method revealed fluctuations of LCP-induced residual stress at sub-mm scale that are consistent with fluctuations in the height of the peened surface.

To investigate the improvement in the fatigue strength of magnesium alloy by peening methods, magnesium alloy AZ31 was treated by submerged laser peening (SLP), cavitation peening (CP), and shot peening (SP), and the fatigue properties were evaluated by a plane bending fatigue test. In the case of SLP, both the impact induced by laser ablation (LA) and that caused by laser cavitation (LC), which developed after LA, were used. In the present study, the fatigue life at a constant bending stress was examined to determine the suitable coverage. It was found that the fatigue strengths at N = 107 for the SLP, CP, and SP specimens treated by each optimum condition were 56%, 18%, and 16% higher, respectively, than that of the non-peened (NP) specimen, which was 97 MPa. The key factors in the improvement of fatigue strength by peening methods were work hardening and the introduction of compressive residual stress.

One of the traditional methods used to improve the fatigue properties of metallic materials is shot peening. More recently, cavitation peening, in which the surface is treated using cavitation impact, has been developed, and the improvements this makes to the fatigue life and the strength of metallic materials have been reported. In order to clarify the difference between these two methods, stainless steel SUS316 L samples were treated by shot peening and cavitation peening, and the fatigue properties of the samples were evaluated utilizing a displacement controlled plane bending fatigue test. The residual stress and hardness before and after the fatigue test were measured, and the surface roughness of each specimen was also measured. It was concluded that the fatigue life of shot peened specimens at bending stress σa > 450 MPa was longer than that of cavitation peened specimens; however, the fatigue strength of the cavitation peened specimens was slightly larger than that of the shot peened specimens. The compressive residual stress introduced by both peening methods decreased during the fatigue test. The reduction in the compressive residual stress in the shot peened specimens was greater than in the cavitation peened specimens, and after the fatigue test, the compressive residual stress in the shot peened specimens was greater than that in the cavitation peened specimens. It was found that the fatigue strength corresponded well with the yield stress estimated from the Vickers hardness corrected by the residual stress obtained after the fatigue test.

One of the traditional methods used to improve the fatigue properties of metallic materials is shot peening. More recently, cavitation peening, in which the surface is treated using cavitation impact, has been developed, and the improvements this makes to the fatigue life and the strength of metallic materials have been reported. In order to clarify the difference between these two methods, stainless steel SUS316 L samples were treated by shot peening and cavitation peening, and the fatigue properties of the samples were evaluated utilizing a displacement controlled plane bending fatigue test. The residual stress and hardness before and after the fatigue test were measured, and the surface roughness of each specimen was also measured. It was concluded that the fatigue life of shot peened specimens at bending stress σa > 450 MPa was longer than that of cavitation peened specimens; however, the fatigue strength of the cavitation peened specimens was slightly larger than that of the shot peened specimens. The compressive residual stress introduced by both peening methods decreased during the fatigue test. The reduction in the compressive residual stress in the shot peened specimens was greater than in the cavitation peened specimens, and after the fatigue test, the compressive residual stress in the shot peened specimens was greater than that in the cavitation peened specimens. It was found that the fatigue strength corresponded well with the yield stress estimated from the Vickers hardness corrected by the residual stress obtained after the fatigue test.

Abstract Background Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. Methods We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. Results HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p

Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.