Intravenous calcitriol administration improves the liver redox status and attenuates ferroptosis in mice with high-fat diet-induced obesity complicated with sepsis.

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.

Calcitriol attenuates poly(I:C)-induced lung injury in obese mice via modulating toll-like receptor 3- and renin-angiotensin system-associated signal pathways.

This study investigated the effects of calcitriol on polyinosinic-polycytidylic acid (poly(I:C))-induced acute lung injury (ALI) and its association with Toll-like receptor 3 (TLR3) and renin-angiotensin system (RAS) signal pathways in obese mice. Normal mice were fed a high-fat diet to induce obesity. Obese mice were divided into four groups: SS group, intratracheally instilled with saline and intravenous (IV) saline injection via tail vein; SD group, instilled with saline and IV calcitriol injection; PS group, instilled with poly(I:C) and IV saline injection; and PD group, instilled with poly(I:C) and IV calcitriol injection. All mice were sacrificed 12 or 24 h after poly(I:C) stimulation. The results showed that poly(I:C) instillation led to increased production of systemic inflammatory cytokines. In the lungs, the population of macrophages decreased, while more neutrophils were recruited. TLR3-associated genes including IRF3, nuclear factor-κB, interferon-ß and phosphorylated IRF3 expression levels, were upregulated. The RAS-associated AT1R and ACE2 protein levels increased, whereas AT2R, Ang(1-7), and MasR levels decreased. Also, reduced tight junction (TJ) proteins and elevated lipid peroxide levels were observed 24 h after poly(I:C) stimulation. Compared to the PS group, the PD group exhibited reduced systemic and lung inflammatory cytokine levels, increased macrophage while decreased neutrophil percentages, downregulated TLR3-associated genes and phosphorylated IRF3, and polarized toward the RAS-AT2R/Ang(1-7)/MasR pathway in the lungs. Higher lung TJ levels and lower injury scores were also noted. These findings suggest that calcitriol treatment after poly(I:C) instillation alleviated ALI in obese mice possibly by downregulating TLR3 expression and tending toward the RAS-associated anti-inflammatory pathway.

Robotic and laparoscopic right lobe living donation compared to the open approach: A multicenter study on 1194 donor hepatectomies.

Due to the success of minimally invasive liver surgery, laparoscopic and robotic minimally invasive donor hepatectomies (MIDH) are increasingly performed worldwide. We conducted a retrospective, multicentre, propensity score-matched analysis on right lobe MIDH by comparing the robotic, laparoscopic, and open approaches to assess the feasibility, safety, and early outcomes of MIDHs. From January 2016 until December 2020, 1194 donors underwent a right donor hepatectomy performed with a robotic (n = 92), laparoscopic (n = 306), and open approach (n = 796) at 6 high-volume centers. Donor and recipients were matched for different variables using propensity score matching (1:1:2). Donor outcomes were recorded, and postoperative pain was measured through a visual analog scale. Recipients' outcomes were also analyzed. Ninety-two donors undergoing robotic surgery were matched and compared to 92 and 184 donors undergoing laparoscopic and open surgery, respectively. Conversions to open surgery occurred during 1 (1.1%) robotic and 2 (2.2%) laparoscopic procedures. Robotic procedures had a longer operative time (493 ± 96 min) compared to laparoscopic and open procedures (347 ± 120 and 358 ± 95 min; p < 0.001) but were associated with reduced donor blood losses ( p < 0.001). No differences were observed in overall and major complications (≥ IIIa). Robotic hepatectomy donors had significantly less pain compared to the 2 other groups ( p < 0.001). Fifty recipients of robotic-procured grafts were matched to 50 and 100 recipients of laparoscopic and open surgery procured grafts, respectively. No differences were observed in terms of postoperative complications, and recipients' survival was similar ( p =0.455). In very few high-volume centers, robotic right lobe procurement has shown to be a safe procedure. Despite an increased operative and the first warm ischemia times, this approach is associated with reduced intraoperative blood losses and pain compared to the laparoscopic and open approaches. Further data are needed to confirm it as a valuable option for the laparoscopic approach in MIDH.

Decreased B4GALT1 promotes hepatocellular carcinoma cell invasiveness by regulating the laminin-integrin pathway.

Beta1,4-galactosyltransferases (B4GALTs) play a crucial role in several diseases, including cancer. B4GALT1 is highly expressed in the liver, and patients with mutations in B4GALT1 exhibit hepatopathy. However, the role of B4GALT1 in liver cancer remains unclear. Here, we found that B4GALT1 was significantly downregulated in hepatocellular carcinoma (HCC) tissue compared with the adjacent liver tissue, and low B4GALT1 expression was associated with vascular invasion and poor overall survival in patients with HCC. Additionally, silencing or loss of B4GALT1 enhanced HCC cell migration and invasion in vitro and promoted lung metastasis of HCC in NOD/SCID mice. Moreover, B4GALT1 knockdown or knockout increased cell adhesion to laminin, whereas B4GALT1 overexpression decreased the adhesion. Through a mass spectrometry-based approach and Griffonia simplicifolia lectin II (GSL-II) pull-down assays, we identified integrins α6 and ß1 as the main protein substrates of B4GALT1 and their N-glycans were modified by B4GALT1. Further, the increased cell migration and invasion induced by B4GALT1 knockdown or knockout were significantly reversed using a blocking antibody against integrin α6 or integrin ß1. These results suggest that B4GALT1 downregulation alters N-glycosylation and enhances the laminin-binding activity of integrin α6 and integrin ß1 to promote invasiveness of HCC cells. Our findings provide novel insights into the role of B4GALT1 in HCC metastasis and highlight targeting the laminin-integrin axis as a potential therapeutic strategy for HCC with low B4GALT1 expression.

Potential therapeutic implications of calcitriol administration and weight reduction on CD4 T cell dysregulation and renin angiotensin system-associated acute lung injury in septic obese mice.

This study investigated the effects of weight reduction and/or calcitriol administration on regulating CD4 T cell subsets and renin-angiotensin system (RAS)-associated acute lung injury (ALI) in obese mice with sepsis. Half of the mice were fed a high-fat diet for 16 weeks, half of them had high-fat diet for 12 weeks then were transferred to a low-energy diet for 4 weeks. After feeding the respective diets, cecal ligation and puncture (CLP) were performed to induce sepsis. There were four sepsis groups: OSS group, obese mice injected with saline; OSD group, obese mice given calcitriol; WSS group, mice with weight reduction and saline; WSD group, mice with weight reduction and calcitriol. Mice were sacrificed after CLP. The findings showed that CD4 T subsets distribution did not differ among the experimental groups. Calcitriol-treated groups had higher RAS-associated AT2R, MasR, ACE2, and angiopoietin 1-7 (Ang(1-7)) levels in the lungs. Also, higher tight junction proteins were noted 12 h after CLP. At 24 h post-CLP, weight reduction and/or calcitriol treatment reduced plasma inflammatory mediator production. Calcitriol-treated groups had higher CD4/CD8, T helper (Th)1/Th2 and lower Th17/regulatory T (Treg) ratios than the groups without calcitriol. In the lungs, calcitriol-treated groups had lower AT1R levels, whereas the RAS anti-inflammatory protein levels were higher than those groups without calcitriol. Lower injury scores were also noted at this time point. These findings suggested weight reduction decreased systemic inflammation. However, calcitriol administration produced a more-balanced Th/Treg distribution, upregulated the RAS anti-inflammatory pathway, and attenuated ALI in septic obese mice.

Glutamine and leucine administration attenuates muscle atrophy in sepsis.

AIMS: This study investigated whether l-glutamine (Gln) and/or l-leucine (Leu) administration could attenuate muscle atrophy in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. MATERIALS AND METHODS: Septic mice were given a daily intraperitoneal injection of Gln, Leu, or Gln plus Leu, and mice were sacrificed on either day 1 or 4 after CLP. Blood and muscles were collected for analysis of amino acid contents and markers related to protein degradation, muscle regeneration, and protein synthesis. KEY FINDINGS: Leu treatment alone increased both muscle mass and total muscle protein content on day 4 after CLP. Gln administration reduced muscular Gln contents on day 1 and enhanced plasma Gln levels on day 4. Higher plasma branched-chain amino acid (BCAA) abundances and lower muscular BCAA levels were observed in Leu-treated mice on day 4. Gln and Leu individually suppressed muscle expressions of the E3 ubiquitin ligase genes, Trim63 and Fbxo32, on day 4 after CLP. As to muscle expressions of myogenic genes, both Gln and Leu upregulated Myog expression on day 1, but Leu alone enhanced Myf5 gene expression, whereas Gln plus Leu increased MyoD and Myog expression levels on day 4. Akt/mammalian target of rapamycin (mTOR) signaling was only activated by Gln and Leu when individually administered. SIGNIFICANCE: Gln and/or Leu administration reduces sepsis-induced muscle degradation and promotes myogenic gene expressions. Leu treatment alone had more-pronounced effects on maintaining muscle mass during sepsis. A combination of Gln and Leu failed to show synergistic effects on alleviating sepsis-induced muscle atrophy.

Effects of different routes and forms of vitamin D administration on CD4+ T cell homeostasis and renin-angiotensin system-associated lung injury in obese mice complicated with polymicrobial sepsis.

This study investigated the impacts of enteral cholecalciferol and/or intravenous calcitriol administration on the balance of cluster of differentiation 4-positive T cell subsets, the renin-angiotensin system (RAS), and the severity of acute lung injury (ALI) in obese mice with sepsis. Mice were fed a high-fat diet and then cecal ligation and puncture (CLP) was performed. Obese mice were divided into four sepsis groups: without vitamin D (VD) (S), with oral cholecalciferol 1 d before CLP (G), with intravenous calcitriol 1 h after CLP (V), and with both cholecalciferol before and intravenous calcitriol after CLP (GV). Mice were euthanized after CLP. The V and GV groups showed higher blood T helper (Th)1/Th2 and lower Th17/T regulatory (Treg) ratios than did the S and G groups. In the lungs, The V group had the lowest nuclear factor-κB and interleukin-1ß gene expressions among all groups 24 h post-CLP. In parallel, gene expressions of angiotensin type 2 receptor (AT2R), angiotensin-converting enzyme 2 (ACE2), and Mas receptor (MasR) were highest in the V group compared to other groups. The protein levels of MasR in the GV group and the AT2R/AT1R ratio in the V group were higher than those in the G and/or S groups. All of the VD-treated groups had lower injury scores than the S group. These findings suggest that calcitriol administration had more-pronounced impacts on regulating the homeostasis of Th/Treg cells and is prone to RAS-associated anti-inflammatory pathway in the lungs. However, both forms of VD attenuated sepsis-induced ALI in obese animals.

Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis.

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways.

Long-Term Survival of Combined Hepatocellular-Cholangiocarcinoma: A Nationwide Study.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an aggressive primary liver cancer. However, the clinical features are not clearly understood because of limited literature and the complex nature of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS: The records of 100,754 patients with newly diagnosed liver cancer between 2004 and 2013 were obtained from the Taiwan Cancer Registry. The primary outcome measures were overall survival and local recurrence-free survival. The median follow-up time was 60 months (29-120 months). RESULTS: HCC-CC tended to share some characteristics with HCC, including increased frequency of stage I cases, high individual tumor rates, and similar patterns of viral hepatitis B and hepatitis C infections. In contrast, HCC-CC showed malignant behavior similar to that of CC, as high-grade tumor cell differentiation and presentation of jaundice were predominant in HCC-CC and CC compared with HCC. Overall survival and local recurrence-free survival rates of HCC-CC were between HCC and CC rates. The mortality rate of HCC-CC was 79.2% (HCC, 77.5%; CC, 93.5%) and the local recurrence rate of HCC-CC was 65.3% (HCC, 74.6%; CC, 88.4%). Surgical treatment was an independent factor for the long-term prognosis of HCC-CC, whereas transarterial chemoembolization (TAcE) promoted survival in both surgical and nonsurgical groups. CONCLUSION: Our data confirmed that, although it reflects the malignant behavior of CC, HCC-CC should mainly be characterized as a subtype of HCC. With careful selection of patients, curative resection and TAcE might benefit the survival of patients with HCC-CC. IMPLICATIONS FOR PRACTICE: Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare cancer that shares demographic characteristics, as well as survival probabilities, with both hepatocellular carcinoma and cholangiocarcinoma. It occurs frequently in patients with hepatitis B virus infection, cirrhotic liver background, and early-stage disease. Compared with 20% of initial resection rates of its counterparts, HCC-CC has higher initial resection rate (55%). Although short-term overall survival is inferior to HCC, its long-term overall survival is similar with HCC.

Effects of the Glutamine Administration on T Helper Cell Regulation and Inflammatory Response in Obese Mice Complicated with Polymicrobial Sepsis.

This study investigated the impacts of GLN on inflammation and T cell dysregulation in obese mice complicated with sepsis. Mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat and was administered for 10 weeks to induce obesity. Mice fed with a high-fat diet were then assigned to sham (SH) and sepsis with saline (SS) or GLN (SG) groups. The SH group was subjected to laparotomy, while the sepsis group underwent cecal ligation and puncture (CLP). The SS group was intravenously injected with saline. The SG group was intravenously administered GLN after CLP. Mice were sacrificed at 12, 24, or 48 h post-CLP, respectively. Results demonstrated that in the presence of obesity, sepsis drove CD4+ T cells toward the helper T (Th)2 and Th17 lineages. Also, expressions of inflammatory cytokines and macrophage infiltration markers in adipose tissues and lungs were elevated. Treatment of obese mice with GLN after sepsis reversed Th polarization and downregulated macrophage infiltration and inflammatory cytokine, whereas the tight junction-associated protein expression increased in the lungs. These findings suggest that the intravenous administration of GLN to obese mice after sepsis modulated a more balanced Th cell lineage, alleviated inflammation, and attenuated lung injury.

Intravenous Glutamine Administration Improves Glucose Tolerance and Attenuates the Inflammatory Response in Diet-Induced Obese Mice after Sleeve Gastrectomy.

Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.

Population-based matching comparison between radiofrequency ablation and percutaneous ethanol or acetic acid injection for hepatocellular carcinoma.

BACKGROUND: Loco-regional therapies are evolving for hepatocellular carcinoma (HCC) treatment. Radiofrequency ablation (RFA) has changed the landscape in treating HCC; however, percutaneous ethanol or acetic acid injection (PEI/PAI) remains a widely used and easily performed technique by experienced clinicians. Nevertheless, the effectiveness of RFA compared to that of PEI/PAI remains unclear. METHODS: Records of 73,136 patients with newly diagnosed HCC between 2007 and 2013 were drawn from the Taiwan Cancer Registry. The primary outcome measures were the overall survival and local recurrence-free survival. Propensity score matching (PSM) was performed to compare the effectiveness of RFA and PEI. Median follow-up time was 61.6 months (36-120 months). RESULTS: After PSM, 4496 patients diagnosed with stage I-III HCC, who were initially treated with RFA (3372 patients) or PEI/PAI (1124 patients), were assessed. Compared to PEI/PAI, patients treated with RFA had better 5- and 9-year overall survival, cancer-specific survival, disease-free survival, and local recurrence-free survival. Median overall survival and recurrence-free survival of patients treated with RFA vs PEI/PAI were 61.5 vs 41.9 months and 72.1 vs 45.2 months, respectively. Multivariate Cox model analysis revealed that, except for patients with high cell grade or advanced stage, RFA resulted in better overall survival (HR: 0.74, 95% CI 0.68-0.81, P < 0.001) and local recurrence-free survival (HR: 0.69, 95% CI 0.63-0.75, P < 0.001) than PEI/PAI. CONCLUSIONS: RFA provides advantages over conventional PEI/PAI for HCC. Considering technological advances in instruments, loco-regional therapies for HCC can be employed in carefully selected patients.

A Prospective Assessment of the Diagnostic Value of Contrast-Enhanced Ultrasound, Dynamic Computed Tomography and Magnetic Resonance Imaging for Patients with Small Liver Tumors.

AIM: This prospective study assessed the diagnostic value of contrast-enhanced ultrasound (CEUS) using long Kupffer phase enhancement for adults with liver tumor size of less than 3 cm. Performance comparisons were also conducted with dynamic computed tomography (CT) and magnetic resonance imaging (MRI). BACKGROUND: CEUS has emerged as a reliable image modality, since the development of second-generation contrast medium with long Kupffer phase enhancement. Nonetheless, dynamic CT and MRI are currently the standard imaging tools for the diagnosis of liver cancers, and the diagnostic value of CEUS for liver cancer has yet to be universally accepted. METHODS: Sixty-six adult patients suspected of having liver tumors smaller than 3 cm underwent CEUS, dynamic CT, and MRI examinations independently. Subsequent tumor biopsies were used to verify the diagnostic performance of the three imaging modalities. RESULTS: The diagnostic odds ratio (DOR, 95% CI) for hepatocellular carcinoma were as follows: CEUS (52.8, 11.4-243), CT (29.29, 7.36-116), and MRI (19.43, 5.44-69.4); for metastasis: CEUS (200, 19.1-2095), CT (24, 5.05-114), and MRI (32, 6.56-156); and all liver malignancy: CEUS (260, 12.7-5310), CT (2.57, 0.55-12.1), and MRI (5.22, 1.25-21.8). CEUS achieved the best differentiation performance. CONCLUSIONS: CEUS outperformed dynamic CT and MRI in terms of diagnostic performance when dealing with small liver tumors (<3 cm).

Effects of prophylactic administration of glutamine on CD4+ T cell polarisation and kidney injury in mice with polymicrobial sepsis.

The present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.

Is robotic hepatectomy cost-effective? In view of patient-reported outcomes.

BACKGROUND: Robotic hepatectomy has been accepted as an alternative for patients needing surgery. However, few reports addressed the patient-reported outcomes and long-term quality of life (QoL) of patients having undergone robotic liver surgery. METHODS: This study presented the QoL and cost-effectiveness associated with robotic and open hepatectomy by performing a comparative survey using two standardized questionnaires (Short Form-36 and Gastrointestinal Quality of Life Index). RESULTS: One hundred patients completed the study. The robotic group tended to experienced longer operation time but shorter length of hospital stay compared to open group. Moreover, the robotic group had faster return to daily activities, less need of patient-controlled anesthesia, and less wound-related complaints in long-term follow-up. The robotic group incurred higher peri-operative expenses; however, the cost of inpatient care was lower. CONCLUSIONS: Our study suggested that robotic hepatectomy provided good post-operative QoL and recovery of daily activity. However, efforts for lowering the financial burden of medical care by reducing the cost of robotic surgery is necessary for further application.

Antecedent Administration of Glutamine Benefits the Homeostasis of CD4+ T Cells and Attenuates Lung Injury in Mice With Gut-Derived Polymicrobial Sepsis.

BACKGROUND: Sepsis is a syndrome with CD4+ T-cell dysfunction and dysregulation of T helper (Th) and regulatory T (Treg) cells. Glutamine (Gln) is a nutrient with immunomodulatory properties. This study investigated the effects of dietary Gln pretreatment on Th and Treg cell homeostasis and lung injury in mice with gut-derived polymicrobial sepsis. METHODS: Mice were randomly assigned to 4 groups with 2 control (C and G) and 2 sepsis groups (SC and SG). The C and SC groups were fed a common semipurified diet, whereas the G and SG groups received an identical diet except that part of the casein was replaced by Gln. Mice were administered these diets for 2 weeks. Then mice in the control groups underwent a sham operation, whereas operations in the sepsis groups were performed with cecal ligation and puncture. Mice were killed 24 hours after the surgery. Blood, spleens, and lungs were collected for further examination. RESULTS: Sepsis resulted in a decreased blood T-lymphocyte percentage, whereas percentages of interferon-γ-expressing, interleukin (IL)-4-expressing, and IL-17-expressing CD4+ T cells were upregulated. Compared with the SC group, Gln administration before sepsis reduced blood Th1, Th2, and Th17 but increased Treg percentages. Also, percentages of CD69-expressing CD4+ and CD8+ cells in the spleen increased. Concomitant with the decreased plasma IL-6 and keratinocyte-derived chemokine levels, the SG group exhibited a lower injury score of the lungs. CONCLUSIONS: Pretreatment with Gln may elicit more balanced Th polarization, alleviate inflammatory response, and attenuate lung injury induced by polymicrobial sepsis.

Therapeutic Potential of Plasma Proteins Derived from Umbilical Cord Blood for Acute Liver Failure.

There are very limited clinically viable treatment options for acute liver failure, a life-threatening condition that rapidly progresses to loss of liver function. In this study, we aim to evaluate the therapeutic potential of UCBP for acute liver failure induced in a rat model by D-galactosamine (GalN). F344 rats were randomly divided into two groups (control and UCBP-treated) after GalN injection. The therapeutic effects of UCBP were evaluated based on survival rate, H&E staining, TUNEL, PCNA staining, and in vivo BrdU labeling. Hepatocyte proliferation and the therapeutic mechanisms of UCBP were examined with BrdU and Western blot assay in vitro. The survival rate in the UCBP-treated group was found to be increased compared to the control group (85 vs 55%, P = 0.029). UCBP treatment significantly decreased apoptosis and increased cell proliferation. These effects may be secondary to specific bioactive molecules in UCBP. In vitro experiments revealed that adiponectin is one of the key biologically active components of UCBP in facilitating this result and promoting hepatocyte proliferation. Furthermore, this effect is mediated by p38/ERK mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, this uncomplicated and clinically accessible approach may serve as effective bridge therapy for acute liver failure.

Toward a fully robotic surgery: Performing robotic major liver resection with no table-side surgeon.

BACKGROUND: Evidence has suggested that robotic system helps perform more major liver resections. However, the required table-side surgeon has remained a concern because of the uncertain performance and the incomplete control of console surgeon. METHODS: Data were reviewed for consecutive 333 robotic liver resections, of which 56 patients underwent left liver resection with the usual setting, and 35 with no table-side surgeon. RESULTS: No conversion was required in the setting with no table-side surgeon. The group without the table-side surgeon had similar complication rates, blood loss, and operative time compared with that of the normal settings, as well as focused analysis on major left hemihepatectomy. CONCLUSION: Our data suggest that performing robotic major liver resection without the presence of the table-side surgeon is safe and feasible. The concise performance of robotic platforms might accelerate the machine learning process along with the ability to predict patterns of future autonomous surgery.

Robotic-assisted right posterior segmentectomies for liver lesions: single-center experience of an evolutional method in left semi-lateral position.

Despite the popularity of minimally invasive surgery (MIS) for hepatectomy, limitations in the approach of the right posterior section of the liver remain. Although skills and approach techniques have been developed for hepatectomy of lesions in the posterior segments of the liver, most are performed laparoscopically and are limited to few experienced hands using rigid laparoscopic instruments. In this study, we tried a different approach area via the aid of a flexible robotic system. Since 2012, we have successfully completed more than 200 robotic hepatectomy procedures in our institution. Two different patient settings have been applied for right posterior segment lesions, including supine position as general setting in early cases and left semi-lateral decubitus setting in our later cases. The demographic data and perioperative outcomes between the two groups were analyzed in regard to different positioning. A total of 25 patients with right posterior segment lesions underwent robotic-assisted resection, 13 were placed in supine position and 12 in left semi-lateral position. The left semi-lateral group had significantly shorter operation time (306.0 versus 416.8 min, p = 0.023), less blood loss (203.9 versus 1092.3 mL, p = 0.030), and lower transfusion rates (0 versus 46.2%, p = 0.015). We described an evolutionary technique for robotic right posterior segmentectomies with the patient placed in left semi-lateral position. This method can be applied for most patients easily and is demonstrated as a safe and feasible approach in selected patients owing to its ability to overcome the difficulty of MIS hepatectomy for right posterior lesions.

Use of robotics in liver donor right hepatectomy.

Liver transplantation is the best solution for end stage liver disease, and has been widely accepted and rapidly developed in the past decades. Along with the improved outcomes of liver transplantation, living-related donor transplantation has been conducted to overcome the shortage of the deceased donor. The most important aspects of the living-related liver transplantation are donor safety and fast recovery after graft procurement. Meanwhile, the rapid progress of minimally invasive surgery (MIS) in general surgery has generated heated debate regarding the appropriateness of MIS in living-related donor graft hepatectomy. Technical innovations and instrument enhancements have been allowing recruitment of more potential candidates through smaller wounds and better surgical experience. Although MIS has been documented with safety and feasibility in complex liver surgery, the progress is slow in regard to the application of MIS in donor graft hepatectomy. Pioneer surgeons have devoted themselves to develop the pure MIS approach for the liver donor surgery, but the steep learning curve for pure MIS major hepatectomy remains a major barrier for wide adoption. The introduction of robotic system may lower the barrier for entry for practice into MIS donor hepatectomy.