Liver volumetry and liver-regenerative interventions: history, rationale, and emerging tools.

BACKGROUND: Postoperative hepatic insufficiency (PHI) is the most feared complication after hepatectomy. Volume of the future liver remnant (FLR) is one objectively measurable indicator to identify patients at risk of PHI. In this review, we summarized the development and rationale for the use of liver volumetry and liver-regenerative interventions and highlighted emerging tools that could yield new advancements in liver volumetry. METHODS: A review of MEDLINE/PubMed, Embase, and Cochrane Library databases was conducted to identify literature related to liver volumetry. The references of relevant articles were reviewed to identify additional publications. RESULTS: Liver volumetry based on radiologic imaging was developed in the 1980s to identify patients at risk of PHI and later used in the 1990s to evaluate grafts for living donor living transplantation. The field evolved in the 2000s by the introduction of standardized FLR based on the hepatic metabolic demands and in the 2010s by the introduction of the degree of hypertrophy and kinetic growth rate as measures of the FLR regenerative and functional capacity. Several liver-regenerative interventions, most notably portal vein embolization, are used to increase resectability and reduce the risk of PHI. In parallel with the increase in automation and machine assistance to physicians, many semi- and fully automated tools are being developed to facilitate liver volumetry. CONCLUSION: Liver volumetry is the most reliable tool to detect patients at risk of PHI. Advances in imaging analysis technologies, newly developed functional measures, and liver-regenerative interventions have been improving our ability to perform safe hepatectomy.

Cambios fisiopatológicos y complicaciones de las resecciones hepáticas / Physiopathological changes and complications of liver resections / Alterações fisiopatológicas e complicações das ressecções hepáticas

Las modernas técnicas quirúrgicas y anestésicas han permitido ampliar el número de intervenciones quirúrgicas a nivel hepático por diversas patologías. Logrando disminuir su moralidad pero manteniendo al día de hoy elevados niveles de morbilidad. Durante la cirugía hepática se producen cambios hemodinámicos vinculados a la movilización del hígado, a los clampeos y a las pérdidas sanguíneas independientemente de la vía de abordaje. En el postoperatorio las complicaciones o cambios fisiopatológicos derivan de las lesiones producidas por los fenómenos de isquemia y reperfusión; y aquellas producidas por la regeneración hepática. Dicha capacidad depende no solo de la cantidad de hígado remanente sino también de la posible hepatopatía preexistente. La insuficiencia hepática postoperatoria es la complicación más temida y se manifiesta con ictericia, ascitis, encefalopatía y alteraciones en la paraclínica como la hiperbilirrubinemia y descenso del tiempo de protrombina. Las complicaciones quirúrgicas dependen del procedimiento realizado y se dividen principalmente en biliares y vasculares. Las secuelas de las hepatectomías dependen de factores como el estado general del paciente, la presencia hepatopatía, el acto quirúrgico y la cantidad y calidad del hígado remanente.

Modern surgical and anesthetic techniques have made it possible to increase the number of liver surgeries for various pathologies. This has reduced morbidity but still maintains high levels of morbidity. During hepatic surgery, hemodynamic changes related to liver mobilization, clamping and blood loss occur independently of the approach route. In the postoperative period, complications or pathophysiological changes derive from the lesions produced by ischemia and reperfusion phenomena; and those produced by hepatic regeneration. This capacity depends not only on the amount of remaining liver but also on the possible pre-existing hepatopathy. Postoperative liver failure is the most feared complication and manifests with jaundice, ascites, encephalopathy and paraclinical alterations such as hyperbilirubinemia and decreased prothrombin time. Surgical complications depend on the procedure performed and are mainly divided into biliary and vascular. The sequelae of hepatectomies depend on factors such as the patient's general condition, the presence of liver disease, the surgical procedure and the quantity and quality of the remaining liver.

As modernas técnicas cirúrgicas e anestésicas tornaram possível aumentar o número de cirurgias hepáticas para várias patologias. Isto levou a uma diminuição da morbidade, mas ainda mantém altos níveis de morbidade. Durante a cirurgia hepática, ocorrem alterações hemodinâmicas ligadas à mobilização hepática, pinçamento e perda de sangue, independentemente da via de aproximação. No período pós-operatório, complicações ou alterações fisiopatológicas derivam de lesões causadas por fenômenos de isquemia e reperfusão, e aquelas causadas pela regeneração hepática. Esta capacidade depende não apenas da quantidade de fígado restante, mas também de uma possível doença hepática pré-existente. A insuficiência hepática pós-operatória é a complicação mais temida e se manifesta com icterícia, ascite, encefalopatia e alterações paraclínicas, tais como hiperbilirrubinemia e diminuição do tempo de protrombina. As complicações cirúrgicas dependem do procedimento realizado e são divididas principalmente em biliares e vasculares. As seqüelas de hepatectomias dependem de fatores como o estado geral do paciente, a presença de doença hepática, o procedimento cirúrgico e a quantidade e qualidade do fígado restante.

[Is the alpps procedure justified in children?] / Opravdana li operatsiya alpps u detei?

The authors have analyzed the indications and outcomes after ALPPS procedure considering modern literature data devoted to this surgery in pediatric patients. No data on post-resection liver failure, as well as unclear future liver remnant function make it possible to question the feasibility of such procedures in children.

Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis.

BACKGROUND: To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy. METHODS: Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage. RESULTS: Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001). CONCLUSIONS: Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.

Prognostic Role of Hepatorenal Function Indexes in Patients With Ebstein Anomaly.

BACKGROUND: Hepatorenal dysfunction is a risk factor for mortality in patients with chronic tricuspid regurgitation due to acquired heart disease. Ebstein anomaly is the most common cause of primary tricuspid regurgitation in adults with congenital heart disease, but the prevalence and prognostic implications of hepatorenal dysfunction are unknown in this population. OBJECTIVES: The purpose of this study was to determine the risk factors and prognostic implications of hepatorenal dysfunction, as measured primarily by the use of model for end-stage liver disease excluding international normalized ratio (MELD-XI score), as well as looking at other associated factors. METHODS: This was a retrospective study of adults with Ebstein anomaly who received care at Mayo Clinic from 2003 to 2018. RESULTS: Of 692 patients, the median MELD-XI score was 10.2 (interquartile range: 9.4 to 13.3); 53 (8%) died and 3 (0.4%) underwent heart transplant. MELD-XI was an independent predictor of death/transplant (hazard ratio: 1.32; 95% confidence interval: 1.11 to 2.06; p < 0.001). In the subset of patients with serial MELD-XI scores (n = 416), temporal change in MELD-XI score (ΔMELD-XI) was also a predictor of death/transplant. In the subset of patients who underwent tricuspid valve surgery (n = 344), a post-operative improvement in MELD-XI score (ΔMELD-XI) was associated with improved long-term survival. Impaired right atrial (RA) reservoir strain and elevated estimated RA pressure were associated with worse baseline MELD-XI and ΔMELD-XI scores. CONCLUSIONS: Hepatorenal dysfunction is a predictor of mortality in Ebstein anomaly, and RA dysfunction and hypertension are hemodynamic biomarkers that can identify patients at risk for deterioration in hepatorenal function and mortality. These data highlight the prognostic importance of noncardiac organ-system dysfunction, and provide complementary clinical risk stratification metrics for management of these patients.

Liver damage at admission is an independent prognostic factor for COVID-19.

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.

Indocyanine green clearance of remnant liver (ICG-Krem) predicts postoperative subclinical hepatic insufficiency after resection of colorectal liver metastasis: theoretical validation for safe expansion of Makuuchi's criteria.

BACKGROUND: Multidisciplinary treatment for colorectal liver metastases (CLMs) often includes major hepatectomy for preoperative chemotherapy-related hepatic injury, although the safety limit for resection extent is unclear. We investigated this parameter using the estimated indocyanine green clearance rate (ICG-K) of liver remnants, focusing on postoperative subclinical hepatic insufficiency (PHI). METHODS: Altogether, 225 patients who underwent resection of CLMs were studied. The predictive power of estimated ICG-K of liver remnant (ICG-Krem) for subclinical PHI (peak bilirubin ≥3 mg/dL or refractory ascites) was compared with those of other potential predictors. The suggested safety limit of ICG-Krem ≥0.05 was also assessed. RESULTS: Receiver-operating curve analysis revealed that ICG-Krem [area under the curve (AUC) 0.752, cutoff 0.102] was the best predictor of subclinical PHI (AUC range for others was 0.632-0.668). Makuuchi's criteria corresponded to ICG-Krem 0.10. Subclinical PHI incidence was significantly elevated at ICG-Krem <0.10 (26% vs 8%, p = 0.002), while potentially fatal PHI (peak bilirubin >7 mg/dL) was not observed until down to ICG-Krem of 0.05. CONCLUSIONS: ICG-Krem sensitively predicts subclinical PHI. Liver failure-related death could be avoided so long as ICG-Krem remains at ≥0.05. However, patients with ICG-Krem 0.05-0.10 are at high risk of subclinical PHI and require intensive care postoperatively.

[Meta-analysis of the outcomes of associating liver partition and portal vein ligation for staged hepatectomy versus portal vein embolization for the treatment of liver cancer with insufficient future liver remnant].

Objective: To explore the feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) for the treatment of liver cancer with insufficient future liver remnant (FLR) . Methods: The data regarding the clinical controlled trials in comparison of ALPPS and PVE in liver surgery were collected from the both domestic and international publications searched through the datebases of PubMed, Cochrane Library, Embase, CNKI, and VIP.Meta analysis was performed by RevMan 5.3 software. Results: Total 10 studies with clinical control were analyzed (9 cohort studies and 1 randomized controlled study) .A total of 620 patients were included, with 165 cases in ALPPS group, 455 cases in PVE group.Results of Meta-analysis showed that there was statistically significant difference (P<0.05) between the two groups in the completion rate of two-steps surgery (OR=6.04, 95%CI: 2.97-12.31, Z=4.96) , FLR growth rate (MD=19.91, 95% CI: 8.64-31.18, Z=3.46) , two-steps surgical interval (MD=-30.48, 95%CI: -37.87--23.09, Z=8.09) , and R0 resection rate (OR=2.29, 95%CI=1.07-4.90, Z=2.13) .While there was no significant differences between the two groups in the mortality rate of postoperative within 90-days, postoperative the total complication rates, postoperative liver failure, and total hospital stay (all P>0.05) . Conclusions: Compared to the PVE procedures, ALPPS appears an effective treatment method for liver tumor with insufficient FLR.Therefore, the applications of ALPPS and PVE are limited and depending on further investigation.

Gastrointestinal, Pancreatic, and Hepatic Manifestations of Cystic Fibrosis in the Newborn.

Gastrointestinal, pancreatic, and hepatic signs and symptoms represent the most common presentation of early disease among patients with cystic fibrosis and may be the initial indication of disease. Regardless of whether cystic fibrosis is diagnosed early by newborn screening or later by clinical course, the impact of gastrointestinal, pancreatic, and hepatic manifestations on early life is nearly ubiquitous. Conditions strongly linked with cystic fibrosis, such as meconium ileus and pancreatic insufficiency, must be recognized and treated early to optimize both short- and long-term care. Similarly, less specific conditions such as reflux, poor weight gain, and cholestasis are frequently encountered in infants with cystic fibrosis. In this population, these conditions may present unique challenges in which early interventions may have significant influence on both short- and long-term morbidity and mortality outcomes.

Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients.

BACKGROUND: Although recent advances in surgical techniques and perioperative management have reduced the morbidity and mortality after hepatectomy, hepatic insufficiency after major hepatectomy remains an important concern. This study aimed to clarify the risk factors for post-hepatectomy liver insufficiency. METHODS: We enrolled 103 consecutive patients who underwent major hepatectomy which was defined as resection of four or more segments. Hepatic insufficiency is defined as an increase in serum total bilirubin after hepatectomy of 7 mg/dL or more, or death from multiple organ failure. We compared the patient disposition, demographics, perioperative factors such as surgical method, combined procedure, morbidity and so on between the patients with or without hepatic insufficiency. RESULTS: Hepatic insufficiency occurred in 14 patients (14%) and six of them died during the hospital stay (6%). Risk factors by univariate analysis were the percentage of hepatic parenchyma to be resected (P = .025), combined procedure (P = .008) and postoperative morbidity excluding hepatic insufficiency (P < .001). A combined procedure (P = .036) and postoperative morbidity excluding hepatic insufficiency (P = .002) were a significant risk factor by multivariate analysis. CONCLUSION: Unless remaining liver after hepatectomy has enough volume, combined procedure may account for hepatic insufficiency, which can follow the development of postoperative morbidity.

Nuclear Factor (Erythroid-Derived 2)-Like 2 Regulates the Hepatoprotective Effects of Remote Ischemic Conditioning in Hemorrhagic Shock.

AIMS: Remote ischemic conditioning (RIC) protects against organ ischemia/reperfusion injury in experimental and clinical settings. We have demonstrated that RIC prevents liver and lung inflammation/injury after hemorrhagic shock/resuscitation (S/R). In this study, we used a murine model of S/R to investigate the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in mediating hepatoprotection. RESULTS: The combination of RIC with S/R caused a synergistic rise in Nrf2 and its translocation to the nucleus in the liver. Increased activation of Nrf2 by RIC augmented heme oxygenase-1 (HO-1) and autophagy and exerted hepatoprotection, concurrent with reductions in S/R-induced TNF-α (tumor necrosis factor alpha) and IL-6 (interleukin-6). In Nrf2 knockout (KO) animals, RIC did not exert hepatoprotection, and it failed to upregulate HO-1 and autophagy. Further, resuscitating wildtype (WT) animals with blood from donor WT animals undergoing RIC was hepatoprotective, but not in Nrf2 KO recipient animals. Interestingly, RIC blood from Nrf2 KO donor animals was also not protective when used to resuscitate WT animals, suggesting a role for Nrf2 both in the afferent arm of RIC where protective factors are generated and also in the efferent arm where organ protection is exerted. Finally, RIC plasma prevented oxidant-induced zebrafish mortality, but not in Nrf2a morpholino knockdown fish. INNOVATION: Activation of Nrf2 is an essential mechanism underlying the hepatoprotective effects of RIC. Nrf2 appears to play a role in the afferent limb of RIC protection, as its absence precludes the generation of the protective humoral factors induced by RIC. CONCLUSION: Our studies demonstrate the critical role of Nrf2 in the ability of RIC to prevent organ injury after S/R.

A novel liver retraction method in laparoscopic gastrectomy for gastric cancer.

BACKGROUND: Retracting the lateral liver segment during laparoscopic distal gastrectomy is important for achieving an optimal surgical field. However, excessive force may injure the liver, causing temporary abnormalities of liver function tests after laparoscopic surgery. We developed a new liver retraction method and assessed its safety and utility. PATIENTS AND METHODS: We retrospectively analyzed records in our surgical database of consecutive surgical patients who underwent laparoscopic distal gastrectomy for early gastric cancer. We divided the 229 patients into two groups based on the liver retraction method used, either flexible liver retraction with clipping and suturing (FLICS) or the Nathanson retractor (NR). One-to-one propensity score matching was performed to match patients, resulting in the records of 53 pairs of cases extracted from the database. Operative and postoperative outcomes were assessed, including following the values of serum liver enzymes, total bilirubin, and C-reactive protein until postoperative day 30. RESULTS: There were no significant differences in patient characteristics or preoperative data in the two groups. The retraction method was not changed intraoperatively for any patients. The operative time was significantly shorter in the FLICS group, but the amount of bleeding did not differ. Liver injury was not observed as a result of liver retraction during surgery. In both groups, serum liver enzymes temporarily increased after surgery but improved rapidly thereafter. The postoperative increases in aspartate transaminase, alanine transaminase, and C-reactive protein levels were significantly lower in the FLICS than in the NR group. No serious complications associated with liver retraction were observed in either group. CONCLUSIONS: Our new liver retraction technique provided an optimal surgical field without inducing liver dysfunction. It is a simple, safe, and effective liver retraction technique.

Hepatectomía en 2 tiempos con técnica de ALPPS (Asociación de bipartición hepática con ligadura portal para hepatectomía en 2 tiempos): experiencia y resultados iniciales del Hospital Regional de Talca / 2 stage hepatectomy with ALPPS technique (Liver splitting association) with ligature portal for hepatectomy in 2 times): experience and initial results of the Regional Hospital of Talca

Resumen Introducción: La insuficiencia hepática posoperatoria (IHP) es una causa importante de morbimortalidad posoperatoria en cirugía hepática. Un remanente hepático futuro (RHF) insuficiente es una de las principales causas IHP La asociación de bipartición hepática con ligadura portal para hepatectomía en 2 tiempos (ALPPS) es una técnica relativamente nueva que induce una rápida hipertrofia parenquimatosa reduciendo el tiempo de espera para lograr un volumen hepático adecuado. Nuestro objetivo es comunicar la experiencia y los resultados iniciales de la hepatectomía en 2 tiempos utilizando la técnica de ALLPS. Material y Método: Se incluyeron todos los pacientes en los que se ha realizado una hepatectomía en 2 tiempos utilizando la técnica de ALPPS entre el 1 de junio de 2014 y el 31 de julio de 2016 en la Unidad de Cirugía Digestiva del Hospital Regional de Talca. Resutados: Durante el periodo de estudio, se realizaron 47 hepatectomías en el Hospital Regional de Talca. En 3 casos (6.3%), se realizó una hepatectomía en 2 tiempos utilizando la técnica de ALPPS, en todos ellos se logró una hipertrofia del remanente hepático futuro (RHF) que permitió completar el segundo tiempo sin IHP clínicamente significativa. Conclusión: En nuestra experiencia inicial, la técnica de ALPPS logró aumentar el RHF permitiendo resecar pacientes que inicialmente tenían un RHF insuficiente para ser sometidos a una hepatectomía mayor.

Introduction: Postoperative liver failure (POLF) is a relevant cause of morbimortality after liver surgery. An insufficient future liver remnant (FLR) is one of the main causes of POLF. The association of hepatic bipartition with portal ligation for 2-stage hepatectomy (ALPPS) is a relatively new technique that induces rapid parenchymal hypertrophy reducing the waiting time to achieve adequate FLR. Our aim is to communicate the experience and the initial results of the hepatectomy in 2-stages using the ALLPS technique. Material and Method: All patients in whom a 2-stage hepatectomy using ALPPS technique between June 1, 2014 and July 31, 2016 in the Digestive Surgery Unit of the Hospital Regional of Talca were included. Results: There were 47 hepatectomies performed at the Hospital Regional of Talca. In 3 cases (6.3%), a 2-stage hepatectomy was performed using the ALPPS technique, in all of which a hypertrophy of the future hepatic remnant (RHF) was achieved, which allowed completing the second stage without POLF clinically significant. Conclusion: In our initial experience, the ALPPS technique successfully allowed increase FLR in patients who initially had insufficient FLR to be submitted a major liver resection.

[Aspects of the importance of postoperative hepatoprotector therapy in urgent surgery]. / Aspekty znachimosti posleoperatsionnoi gepatoprotektornoi terapii v urgentnoi khirurgii.

The purpose of this study was to determine the effect on the effectiveness of the correction of enteric insufficiency syndrome in patients with urgent surgical pathology included in the scheme of complex therapy Remaxol. The results of complex therapy of 227 patients (98 people with common peritonitis and 129 patients with acute intestinal obstruction) were analyzed. 128 patients of the main group in the postoperative period were included in the therapy scheme Remaxol: intravenously drip in a daily dose of 400 ml at a rate of 40 drops per minute, a course of -5 days. Patients of the control group (99 people) received standard treatment. The study is devoted to the role of postoperative hepatoprotective therapy in the treatment of patients with urgent surgical pathology. The main attention is paid to the hepatoenteric link of the pathogenesis of polyorganism insufficiency. This approach gives hope for a reduction in the risk of abdominal sepsis and a reduction in mortality among patients with acute abdominal pathology. The study found that in patients with acute abdominal pathology, an increase in the severity of enteric insufficiency syndrome due to toxic aggression and bacterial translocation can lead to hepatic dysfunction. Consequently, the implementation of hepatoprotective therapy is a pathogenetic link in the complex treatment of urgent surgical patients. The obtained results allowed to draw a number of conclusions. In particular, it has been established that the use of hepatoprotective therapy in the complex medical treatment of patients with acute abdominal pathology makes it possible to stop hepatorenal syndrome by the 5th day, and the syndrome of enteric insufficiency by the 7th day. Earlier relief of hepatic dysfunction and enteral insufficiency syndrome due to hepatoprotective therapy allowed to reduce the incidence of infectious complications to 9.7%, to reduce the lethality to 9.4% and to shorten hospitalization from 17.29 to 1.734 to 12.14±1.385 bed/day.

Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. METHODS: Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. RESULTS: Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. CONCLUSIONS: Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. LEVEL OF EVIDENCE: Level IV.

[Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) in focal liver diseases management]. / Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) v lechenii ochagovykh obrazovanii pecheni.

AIM: To determine ALPPS advisability in small future remnant liver. MATERIAL AND METHODS: 22 ALPPS procedures were performed at the Center for Surgery and Transplantology for the period from 2011 to 2016. Indications were both tumoral and non-tumoral unresectable liver diseases. Postoperative complications were classified according to Clavien-Dindo, ISGLS. RESULTS: According to CT-volumetry future remnant liver before the 1st stage of ALPPS was from 17 to 25%, before the 2nd stage - from 28 to 49%. Both stages were carried out in all patients with R0-resection in 100%. Postoperative complications were diagnosed in 40.9%, 1 death was caused by severe pulmonary embolism. Follow-up varied from 3 to 48 months (median 17.5), 86% of patients are alive at present. CONCLUSION: ALPPS provides rapid and effective FLR growth and can be used for both tumoral and non-tumoral unresectable liver diseases. However, ALPPS should be performed strictly according to indications and only in specialized centers with extensive experience of advanced liver resection and transplantation after previous comprehensive selection of patients.

Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury in the cholestatic liver through inhibition of high-mobility group box protein b1 (HMGB1) signaling.

BACKGROUND: The objective of this study was to elucidate whether the inhibition of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation) groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was administered 15 minutes before ischemia/reperfusion. We measured intrahepatic Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis, gene expression of inflammation-associated factors, and serum high-mobility group box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was significantly greater in the bile duct ligation group than in the sham group. Toll-like receptor 4 expression was further increased after ischemia/reperfusion in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic markers were significantly greater in both the sham ischemia/reperfusion and bile duct ligation ischemia/reperfusion groups than in the groups without ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group than in the sham group and was further increased in the bile duct ligation ischemia/reperfusion group. Genomic expression of inflammation-associated factors was also significantly greater in the bile duct ligation ischemia/reperfusion group than in the sham group. Serum high-mobility groups box protein b1 levels were greater in the bile duct ligation ischemia/reperfusion group than in the sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct ligation ischemia/reperfusion group were significantly attenuated by preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a potential to minimize severe injury after ischemia/reperfusion in the cholestatic liver through inhibition of high-mobility groups box protein b1.

Portal Vein Embolization Reduces Postoperative Hepatic Insufficiency Associated with Postchemotherapy Hepatic Atrophy.

BACKGROUND: The risk of postoperative hepatic insufficiency (PHI) is increased among patients with significant postchemotherapy hepatic atrophy. The primary aim of this study was to evaluate whether the liver regeneration stimulated by portal vein embolization (PVE) can protect against PHI. METHODS: Clinicopathological features of 177 patients treated with preoperative chemotherapy followed by PVE and hepatectomy were reviewed. Degree of atrophy was defined as the ratio of percentage difference in total liver volume (estimated by manual volumetry) to standardized liver volume. Kinetic growth rate (KGR, degree of hypertrophy [absolute % change in future liver remnant volume] divided by the number of weeks after PVE) and PHI events were compared between patients with degree of atrophy <10 vs ≥10%. Risk factors for the PHI were assessed using logistic regression. RESULTS: Seventy patients (40%) experienced significant hepatic atrophy ≥10% following preoperative chemotherapy. PHI rates were not significantly increased in patients who experienced significant hepatic atrophy (5.6 vs 8.6%, P = 0.443). KGR <2%/week (odds ratio, 8.10, P = 0.037) was the sole independent preoperative predictor of PHI. KGR ≥2% was associated with decreased PHI in both patients with <10% atrophy (0 vs 9.5%, P = 0.035) and ≥10% atrophy (2.6 vs 16.0%, P = 0.044). CONCLUSIONS: Even in high-risk patients with ≥10% degree of atrophy from preoperative chemotherapy, KGR ≥2% mitigates the deleterious effects of hepatic atrophy and significantly reduces PHI to almost zero. In these high-risk patients, PVE with KGR calculation remains the most important preoperative technique to reduce liver failure after major hepatectomy.

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

BACKGROUND: It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. MATERIALS AND METHODS: Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. RESULTS: Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. CONCLUSIONS: HHOS has protective effects against liver injury in a rat model of HSR.