Comparing iodized oil with polyvinyl alcohol for portal vein embolization in promoting liver remnant increase before partial hepatectomy.

BACKGROUND: To compare the efficacy and safety of iodized oil versus polyvinyl alcohol (PVA) particles in portal vein embolization (PVE) before partial hepatectomy. METHODS: From October 2016 to December 2021, 86 patients who planned to undergo hepatectomy after PVE were enrolled, including 61 patients post-PVE with PVA particles + coils and 25 patients post-PVE with iodized oil + coils. All patients underwent CT examination before and 2-3 weeks after PVE to evaluate the future liver remnant (FLR). The intercohort comparison included the degree of liver volume growth, changes in laboratory data, and adverse events. RESULTS: There was no significant difference in the resection rate between the iodized oil group and the PVA particle group (68 % vs. 70 %, p = 0.822). In terms of the degree of hypertrophy (9.52 % ± 13.47 vs. 4.03 % ± 10.55, p = 0.047) and kinetic growth rate (4.07 % ± 5.4 vs. 1.55 % ± 4.63, p = 0.032), the iodized oil group was superior to the PVA group. The PVE operation time in the PVA particle group was shorter than that in the iodized oil group (121. 72 min ± 34.45 vs. 156. 2 min ± 71.58, p = 0.029). There was no significant difference in the degree of hypertrophy between the high bilirubin group and the control group (5.32 % ± 9.21 vs. 6.1 % ± 14.79, p = 0.764). Only 1 patient had a major complication. CONCLUSIONS: Compared with PVA particles, iodized oil PVE can significantly increase liver volume and the degree of hypertrophy without any significant difference in safety.

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

Autologous blood transfusion reduces the requirement for perioperative allogenic blood transfusion in patients undergoing major hepatopancreatobiliary surgery: a retrospective cohort study.

INTRODUCTION: Major hepatopancreatobiliary surgery is associated with a risk of major blood loss. The authors aimed to assess whether autologous transfusion of blood salvaged intraoperatively reduces the requirement for postoperative allogenic transfusion in this patient cohort. MATERIALS AND METHODS: In this single centre study, information from a prospective database of 501 patients undergoing major hepatopancreatobiliary resection (2015-2022) was analysed. Patients who received cell salvage ( n =264) were compared with those who did not ( n =237). Nonautologous (allogenic) transfusion was assessed from the time of surgery to 5 days postsurgery, and blood loss tolerance was calculated using the Lemmens-Bernstein-Brodosky formula. Multivariate analysis was used to identify factors associated with allogenic blood transfusion avoidance. RESULTS: 32% of the lost blood volume was replaced through autologous transfusion in patients receiving cell salvage. Although the cell salvage group experienced significantly higher intraoperative blood loss compared with the noncell salvage group (1360 ml vs. 971 ml, P =0.0005), they received significantly less allogenic red blood cell units (1.5 vs. 0.92 units/patient, P =0.03). Correction of blood loss tolerance in patients who underwent cell salvage was independently associated with avoidance of allogenic transfusion (Odds ratio 0.05 (0.006-0.38) P =0.005). In a subgroup analysis, cell salvage use was associated with a significant reduction in 30-day mortality in patients undergoing major hepatectomy (6 vs. 1%, P =0.04). CONCLUSION: Cell salvage use was associated with a reduction in allogenic blood transfusion and a reduction in 30-day mortality in patients undergoing major hepatectomy. Prospective trials are warranted to understand whether the use of cell salvage should be routinely utilised for major hepatectomy.

Use of local wound infiltration in open hepatectomy to reduce wound pain: A systematic review and meta-analysis.

The aim of this study was to assess the effects of local wound infiltration anaesthesia on postoperative wound pain in patients undergoing open liver resection. The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang databases were searched. The search period spanned from database creation to December 2022. All relevant studies on local wound infiltration anaesthesia for analgesia after hepatectomy were included. Two investigators independently screened the literature, extracted data and evaluated the quality of each study. Review Manager (RevMan) 5.4 software (Cochrane Collaboration) was used for the meta-analysis, in which 12 studies with 986 patients were included. The results show that local wound infiltration anaesthesia effectively reduced surgical site wound pain at 4 h (mean difference [MD]: -1.26, 95% confidence intervals [CIs]: -2.15 to -0.37, P = .005), 12 h (MD: -0.84, 95% CIs: -1.26 to -0.42, P < .001), 24 h (MD: -0.57, 95% CIs: -1.01 to -0.14, P = .009) and 48 h (MD: -0.54, 95% CIs: -0.81 to -0.26, P < .001) postoperatively; however, there was no significant difference in analgesia at 72 h postoperatively (MD: -0.10, 95% CIs: -0.80 to 0.59, P = .77). These findings suggest that local wound infiltration anaesthesia administered to patients undergoing open liver resection provides good postoperative wound analgesia at the surgical site.

Significance of Skeletal Muscle Loss in Liver Hypertrophy in Patients Undergoing Portal Vein Embolization Before Major Hepatectomy: Assessment With Body Composition and Nutritional Indicators.

BACKGROUND/AIM: The relationship between body composition including skeletal muscle and liver hypertrophy initiated by portal vein embolization (PVE) for major hepatectomy has not been clarified. This study aimed to investigate the effects of skeletal muscle, body adipose, and nutritional indicators on liver hypertrophy. PATIENTS AND METHODS: Fifty-nine patients who underwent PVE scheduled for major right-sided hepatectomy were included. The skeletal muscle area of L3 as skeletal muscle index was calculated. The relationship between skeletal muscle loss and clinical variables was assessed. We also evaluated the relationship between >30% liver growth or >12% liver growth/week after PVE. RESULTS: Skeletal muscle loss was observed in 39 patients (66.1%) and associated with zinc deficiency, visceral adipose index, liver growth rate, and liver growth rate/week. Multivariate analysis indicated that future liver volume and skeletal muscle index were associated with >30% liver growth, and functional future liver volume and skeletal muscle index were associated with >12% liver growth/week. CONCLUSION: Loss of skeletal muscle, and a small future remnant liver volume, attenuates liver hypertrophy initiated by PVE. Strength building and nutritional supplementation may have positive effects on liver hypertrophy after PVE.

A Pilot Study Evaluating the Effectiveness and Safety of Daikenchuto (TJ-100) for the Treatment of Postoperative Abdominal Pain or Bloating in Patients Undergoing Hepatectomy: Study Protocol for a Randomized, Open, Controlled Trial.

This study is being performed to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms, and to examine the effects of DKT on small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities. This is a randomized, open, controlled trial using patients treated with usual care as the control group. Patients who meet the inclusion criteria are randomized to the study groups. Eligible patients are randomized to the DKT therapy group (DKT administration for 14 days postoperatively or until the day of discharge if a patient leaves the hospital less than 14 days after the surgery) or the usual care group (no administration of DKT (ratio 1:1). Using the NRS (numeric rating scale) as an indicator, we will attempt to show whether DKT is effective for abdominal pain and bloating after surgery by comparing both groups. We will also attempt to evaluate postoperative small intestinal mucosal atrophy using DAO and GLP-2 activities in the serum, and postoperative nutrient absorption using nutrient assessment indicators. This study is being conducted according to the CONSORT statement. A consent form was signed by all participants, and the study protocol has been approved by the Central Review Board and Local Ethics Committee (CRB7180001).

Intravenous iron supplementation after liver surgery: Impact on anemia, iron, and hepcidin levels-a randomized controlled trial.

BACKGROUND: Anemia is a recognized risk factor for perioperative related morbidity and mortality and is frequently reported in liver surgeries with an estimated incidence of 32%. We aim to assess the impact of intravenous iron administration in the immediate postoperative period on anemia and iron status as well as to determine the kinetics of hepcidin after liver surgery. METHODS: The HepciFer trial, a randomized controlled trial, included 50 patients undergoing liver surgery. In accordance with the randomization process, patients received either ferric carboxymaltose (15 mg/kg, maximum 1 g) or placebo 4 hours after surgery. RESULTS: The mean hemoglobin level, 7 days after surgery, did not differ significantly between the intervention and control group (11.1 ± 1.8 g/dL and 10.4 ± 1.6 g/dL, respectively) with a mean difference of +0.7 g/dL ([95% confidence interval, -0.3 to +1.7], P = .173). Within patients receiving intravenous iron supplementation, none presented biological signs of functional iron deficiency. Hepcidin levels remained significantly higher during the observation period in the intervention group. Inflammatory biomarkers, red blood cells transfusion rate and hospital duration of stay were similar between groups. CONCLUSION: Intravenous ferric carboxymaltose administration did not result in a significant increase of hemoglobin levels 7 days after surgery. However, this study suggests that intravenous iron supplementation in the immediate postoperative settings prevents functional iron deficiency. Intravenous iron supplementation overcame the hepcidin-mediated blockade of iron absorption and should be considered as the preferred route of administration in the postoperative period.

Clinical Efficacy of Perioperative Immunonutrition Containing Omega-3-Fatty Acids in Patients Undergoing Hepatectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. METHODS: A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS: Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34-0.95; p = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37-0.75; p = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28-0.89; p = 0.02), and it shortened the length of hospital stay (MD = -3.80, 95% CI: -6.59 to -1.02; p = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32-1.12; p = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55-3.08; p = 0.55), liver failure (OR = 0.54, 95% CI: 0.23-1.24; p = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26-1.83; p = 0.46). CONCLUSION: Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.

Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Prognostic impact of immune-microenvironment in colorectal liver metastases resected after triplets plus a biologic agent: A pooled analysis of five prospective trials.

BACKGROUND: Immune-contexture of tumour microenvironment (TME) influences prognosis of colorectal cancer (CRC) patients and can be altered by cytotoxic and targeted agents. Limited data are available regarding the immune-TME of CRC after treatment. METHODS: An extensive immunohistochemistry evaluation of immunological parameters on tumour cells and TME of colorectal liver metastases from 106 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (5-fluorouracil, oxaliplatin and irinotecan) or COI (capecitabine, oxaliplatin and irinotecan) plus bevacizumab (N = 59) or cetuximab (N = 47) in five first-line no-profit clinical trials was performed. RESULTS: No substantial differences were reported in immunological parameters according to administered targeted agent, RAS/BRAF mutational status and histopathological or Response Evaluation Criteria in Solid Tumours response. Stromal expression of Cyclooxygenase-2 (COX-2) (p = 0.002), Human leukocyte antigen (HLA) (p = 0.003) and Programmed cell death protein 1 (PD1) (p = 0.002) were independent prognostic factors for longer relapse-free survival (RFS) at multivariate analysis with a positive trend for post-resection overall survival (OS). Patients whose metastases expressed stromal COX-2, HLA and PD1 (inflamed-score positive) reported longer RFS (25.5 versus 9.8 months; p < 0.001) and post-resection OS (64.3 versus 37.7 months; p = 0.003) as compared with others. In addition, patients with higher expression of CD4 and CD8 T-cells in tumour core and invasive margin (CD4/CD8-score) showed a better post-resection OS (not-reached versus 41.6 months; p = 0.032). A combined score of inflamed-score and CD4/CD8-score (combo-score) showed a clear prognostic role. CONCLUSIONS: The present study emphasises the role of immune-TME as independent predictor of survival in patients resected after triplets plus biologic. Inflamed-, CD4/C8- and combo-scores should be confirmed as prognostic factors in further studies.

A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases.

INTRODUCTION: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. MATERIAL AND METHODS: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. CONCLUSIONS: In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

Ascitis quilosa en el posoperatorio de hepatectomía derecha / Chylous ascites after right liver resection

La ascitis quilosa posoperatoria (AQP) se debe a acumulación de líquido rico en triglicéridos en la cavidad peritoneal tras una lesión en la cisterna del quilo o en sus afluentes. Es infrecuente verla después de una hepatectomía. Se presenta el caso de un varón de 44 años con adenocarcinoma a 16 cm del margen anal T3N1, con metástasis que ocupaba casi la totalidad del lóbulo hepático derecho. Luego de quimioterapia se realizó hepatectomía derecha, observándose al cuarto día postoperatorio líquido del drenaje endotorácico de aspecto lechoso, con triglicéridos 223 mg/dL y 77 mg/dL de triglicéridos séricos. Se inició dieta sin grasas, hiperproteica, con ácidos grasos de cadena media y octreótide (100 microgramos subcutáneos cada 8 horas), con resolución del cuadro. En conclusión, la complicación quilosa puede tratarse exitosamente con un abordaje menos agresivo, sin suprimir la ingesta oral, utilizando octreótide subcutáneo, dieta exenta de grasas, suplementada con proteínas y ácidos grasos de cadena media.

Postoperative chylous ascites is an intraperitoneal collection of lymphatic fluid enriched with long-chain triglycerides that results from injury of the cisterna chyli or its main tributaries. This complication is rare after liver resections. Here, we report on the case of a 44 year-old man with a T3N1 rectal adenocarcinoma 16 cm above the anal margin, with metastatic compromise of almost the entire right liver lobe. Following chemotherapy, he underwent right liver resection. On postoperative day four, the thoracic drain evidenced milky fluid containing triglyceride 223 mg/dL with serum triglycerides 77 mg/dL. A fat-free diet was indicated with fat-free protein supplements, medium chain triglycerides and octreotide (100 μg subcutaneously every 8 hours), with complete resolution. In conclusion, postoperative chylous complications may be treated successfully by a less aggressive approach, with oral diet, subcutaneous octreotide, fat-free diet supplemented with proteins and medium chain fatty acids.

Preoperative nutritional evaluation of patients with hepatic alveolar echinococcosis.

OBJECTIVE: This study is aimed at determining the preoperative nutritional status of patients with hepatic alveolar echinococcosis (HAE), and subsequently establish a concise and reasonable nutritional evaluation indicator. The established evaluation method could be used for clinical preoperative risk assessment and prediction of post-operation recovery. METHODS: The basic patient information on height, body weight, BMI and hepatic encephalopathy of 93 HAE patients were examined. Subsequently, abdominal ultrasonography, blood coagulation and liver function tests were done on the patients. Liver function was assessed using the Child-Pugh improved grading method while nutritional status was evaluated using the European Nutrition Risk Screening 2002 (NRS 2002) method. Additional parameters including hospitalization time, the hemoglobin (HGB) level on the 3rd day after the operation, and the number of postoperative complications of HAE patients were also recorded. RESULTS: The NRS 2002 score was negatively correlated with body weight, body mass index (BMI)and albumin (ALB) (P<0.01), and positively correlated with the transverse and longitudinal diameters of the lesions (P<0.01). A worse grading of liver function was associated with a low ALB and a high NRS 2002 score (P<0.01). Results of the NRS 2002 score indicate that the hospitalization time of the normal nutrition group was significantly shorter than that of the malnourished group (P < 0.05). The HGB level of the control group on the 3rd day after the operation was significantly higher than that of the malnourished group (P < 0.05), and the number of postoperative complications was lower than that of malnutrition group (P < 0.05). CONCLUSION: Malnutrition is common in HAE patients. The nutritional status of HAE patients is related to many clinical factors, such as Child-Pugh classification of liver function, size of the lesion, and ALB among others. Although both BMI and ALB can be used as primary screening indicators for malnutrition in HAE patients, NRS 2002 is more reliable and prudent in judging malnutrition in HAE patients. Therefore, BMI and ALB are more suitable for preoperative risk assessment and prediction of postoperative recovery.

Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery.

Ischemia-reperfusion (I/R) injury is an unresolved problem in liver resection and transplantation. The preexisting nutritional status related to the gut microbial profile might contribute to primary non-function after surgery. Clinical studies evaluating artificial nutrition in liver resection are limited. The optimal nutritional regimen to support regeneration has not yet been exactly defined. However, overnutrition and specific diet factors are crucial for the nonalcoholic or nonalcoholic steatohepatitis liver diseases. Gut-derived microbial products and the activation of innate immunity system and inflammatory response, leading to exacerbation of I/R injury or impaired regeneration after resection. This review summarizes the role of starvation, supplemented nutrition diet, nutritional status, and alterations in microbiota on hepatic I/R and regeneration. We discuss the most updated effects of nutritional interventions, their ability to alter microbiota, some of the controversies, and the suitability of these interventions as potential therapeutic strategies in hepatic resection and transplantation, overall highlighting the relevance of considering the extended criteria liver grafts in the translational liver surgery.

Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats.

OBJECTIVE: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on liver regeneration of rats with liver cirrhosis after hepatectomy and antifibrosis. MATERIALS AND METHODS: Omega-3 polyunsaturated fatty acids were intravenously injected in n-3 PUFA group 3 days before the operation to 1 day after partial hepatectomy. 70% hepatectomy was performed in rats, which were subsequently divided into 4 groups, namely normal and hepatectomy group (PH); liver cirrhosis and hepatectomy group (LC+PH); liver cirrhosis, n-3 PUFA (1 mL/kg), and hepatectomy group (LC+n-3 PUFA+PH); liver cirrhosis, n-3 PUFA (2 mL/kg) and hepatectomy group (LC+n-3PUFA*+PH). Body/liver weight ratios, serum parameters, histopathological examination, immunostaining, inflammatory cytokine and quantification of mRNA expression were also investigated. RESULTS: Liver regeneration was significantly delayed compared with PH group 7 days after hepatectomy (PH) in LC+PH group. Besides, liver regeneration of LC+n-3 PUFA*+PH group increased significantly compared with LC+PH group 7 days after PH. In LC+PH group, liver cirrhotic was significantly higher compared with LC+n-3 PUFA+PH group 7 days after PH. In the meantime, liver cirrhosis of LC+n-3 PUFA*+PH group was significantly reduced compared with LC+n-3 PUFA+PH group 7 days after PH. Anti-inflammatory cytokine IL-10 was increased and pro-inflammatory cytokine IL-6 was decreased in LC+n-3 PUFA*+PH group compared with LC+PH group. N-3 PUFA also suppressed increments in mRNA expression for transforming growth factor-ß and up-regulated the expression of matrix metalloproteinase-9 and matrix metalloproteinase-1 in the liver. CONCLUSIONS: The mentioned results clearly show that n-3 PUFA reduces liver fibrosis and promotes liver regeneration, even under cirrhotic conditions. This could be a potentially useful treatment for liver cirrhosis.

Laparoscopic versus open two-stage hepatectomy for bilobar colorectal liver metastases: A bi-institutional, propensity score-matched study.

BACKGROUND: The safety and feasibility of laparoscopic, two-stage hepatectomy for bilobar colorectal liver metastases is poorly evaluated. METHODS: We reviewed retrospectively 86 consecutive patients who underwent complete two-stage hepatectomy (left lobe clearance as the first stage and standard/extended right hepatectomy as the second stage) for bilobar colorectal liver metastases between 2007 and 2017 in 2 tertiary centers. Short- and long-term outcomes were compared between laparoscopic and open two-stage hepatectomy before and after propensity score matching. RESULTS: Laparoscopic two-stage hepatectomy was performed in 38 patients and open two-stage hepatectomy in 48. After propensity score matching, 25 laparoscopic and 25 open patients showed similar preoperative characteristics. For the first stage, a laparoscopic approach was associated with lesser hospital stays (4 vs 7.5 days; P < .001). For the second stage, a laparoscopic approach was associated with less blood loss (250 vs 500 mL; P = .040), less postoperative complications (32% vs 60%; P = .047), lesser hospital stays (9 vs 16 days; P = .013), and earlier administration of chemotherapy (1.6 vs 2 months; P = .039). Overall survival, recurrence-free survival, and liver-recurrence-free survival were comparable between the groups (3-year overall survival: 80% vs 54%; P = .154; 2-year recurrence-free survival: 20% vs 18%; P = .200; 2-year liver-recurrence-free survival: 39% vs 33%; P = .269). Although both groups had comparable recurrence patterns, repeat hepatectomies for recurrence were performed more frequently in the laparoscopic two-stage hepatectomy group (56% vs 0%; P = .006). CONCLUSION: Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases is safe and feasible with favorable surgical and oncologic outcomes compared to open two-stage hepatectomy.

Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial.

BACKGROUND: Hepatoblastoma treatment with curative intent requires surgical resection, but only about a third of newly diagnosed patients with hepatoblastoma have resectable disease at diagnosis. Patients who have upfront resection typically receive a total of 4-6 cycles of adjuvant chemotherapy post-surgery, with the combination of cisplatin, fluorouracil, and vincristine. We aimed to investigate whether event-free survival in children with hepatoblastoma who had complete resection at diagnosis could be maintained with two cycles of adjuvant chemotherapy. METHODS: In this Children's Oncology Group, multicentre, phase 3 trial, patients were enrolled in four risk groups on the basis of Evans surgical stage, tumour histology, and levels of α-fetoprotein at diagnosis to receive risk-adapted therapy. Here, we report on the low-risk stratum of the trial. Eligible patients were younger than 21 years and had histologically confirmed, stage I or II hepatoblastoma without 100% pure fetal stage I or small-cell undifferentiated histology; elevated serum α-fetoprotein level (>100 ng/mL); a complete resection at diagnosis; at least 50% Karnofsky (patients >16 years) or Lansky (patients ≤16 years) performance status; and had received no previous chemotherapy or other hepatoblastoma-directed therapy. Patients received two 21-day cycles of cisplatin, fluorouracil, and vincristine within 42 days of resection, consisting of cisplatin (100 mg/m2 per dose or 3·3 mg/kg per dose for children <10 kg) intravenously over 6 h on day 1; fluorouracil (600 mg/m2 per dose or 20 mg/kg per dose for children <10 kg) intravenous push on day 2; and vincristine (1·5 mg/m2 per day to a maximum dose of 2 mg, or 0·05 mg/kg per day for children <10 kg) intravenous push on days 2, 9, and 16. The primary outcome was investigator-assessed event-free survival. As prespecified by protocol, we analysed the primary endpoint 6 years after enrolment (cutoff date June 30, 2017). This trial is registered with ClinicalTrials.gov, number NCT00980460, and is now permanently closed to accrual. FINDINGS: Between May 18, 2010, and May 28, 2014, 51 patients in 32 centres in two countries were enrolled into the low-risk stratum of this trial, of whom 49 received c hemotherapy treatment after surgery and were evaluable for activity and safety. Median follow-up time for all evaluable patients was 42 months (IQR 36-62). 4-year event-free survival was 92% (95% CI 79-97) and 5-year event-free survival was 88% (72-95). Two (4%) of 49 patients had surgical complications (bile leaks). The most common grade 3-4 adverse events were febrile neutropenia in seven (14%) patients, decreased neutrophil count in three (6%) patients, infections in four (8%) patients, and diarrhoea in four (8%) patients. Ototoxicity occurred in one (2%) patient. One (2%) patient of the three who relapsed in this cohort died from disease. Two (4%) patients died in clinical remission after therapy discontinuation. One patient died of pneumonia and bacterial sepsis 1 year after therapy discontinuation and another patient died of unrelated causes 57 months after therapy completion. There were no treatment-related deaths. INTERPRETATION: Minimal postoperative chemotherapy with two cycles of cisplatin, fluorouracil, and vincristine can ensure disease control in patients with hepatoblastoma resected at diagnosis. Our results show that dose reduction of ototoxic agents is a safe, effective treatment for these children. FUNDING: National Institutes of Health.

Effect of ω-3 polyunsaturated fatty acids on liver function and inflammatory reaction in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized control trials.

INTRODUCTION: Several studies have investigated the relationship between ω-3 polyunsaturated fatty acids (PUFAs) administration and liver function and inflammatory reaction in patients undergoing liver resection, but the results remain conflicting and inconclusive. Areas covered: In this meta-analysis, a relevant database search was performed to retrieve all the randomized controlled trials (RCTs) exploring the effect of ω-3 PUFAs administration in patients undergoing hepatectomy until the end of April 2018. A random effect model was used to conduct this meta-analysis with RevMan 5.3.5 software. The quality of evidence for each postoperative outcome was assessed using the GRADEpro analysis. Expert opinion: 4 RCTs including 553 patients (277 with and 276 without ω-3 PUFAs) were identified. ω-3 PUFAs significantly reduced alanine aminotransferase [Mean difference (MD): -68.82, 95% confidence interval (CI): -108.55 to - 29.08; p = 0.0007]; aspartate aminotransferase (MD: -64.92, 95% CI: -112.87 to -16.98; p = 0.008), white blood cell count (MD: -1.22, 95% CI: -2.15 to -0.29; p = 0.01) and increased the level of pre-albumin on postoperative day 3 (MD: 10.42, 95% CI: 4.84 to 15.99; p = 0.0002). The results indicate that ω-3 PUFAs administration has a positive impact on the liver function and inflammatory reaction in patients undergoing liver resection.

Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis.

Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.