Postoperative Liver Regeneration Research Articles

Evaluation of liver regeneration after hemi-hepatectomy by combining computed tomography and post-operative liver function

BackgroundAccurate evaluation of postoperative liver regeneration is essential to prevent postoperative liver failure. AimsTo analyze the predictors that affect liver regeneration after hemi-hepatectomy. MethodPatients who underwent hemi-hepatectomy in Hangzhou First People's Hospital and Hangzhou Shulan Hospital from January 2016 to December 2021 were enrolled in this study. The regeneration index (RI) was calculated by the following equation: RI = [(postoperative total liver volume {TLVpost} - future liver remnant volume {FLRV}/FLRV] × 100 %. Hepatic dysfunction was defined according to the “TBilpeak>7” standard, which was interpreted as (peak) total bilirubin (TBil) >7.0 mg/dL. Good liver regeneration was defined solely when the RI surpassed the median with hepatic dysfunction. Logistic regression analyses were performed to estimate prognostic factors affecting liver regeneration. ResultA total of 153 patients were enrolled, with 33 in the benign group and 120 patients in the malignant group. In the entire study population, FLRV% [OR 4.087 (1.405–11.889), P = 0.010], international normalized ratio (INR) [OR 2.763 (95%CI, 1.008–7.577), P = 0.048] and TBil [OR 2.592 (95%CI, 1.177–5.710), P = 0.018] were independent prognostic factors associated with liver regeneration. In the benign group, only the computed tomography (CT) parameter FLRV% [OR, 11.700 (95%CI, 1.265–108.200), P = 0.030] predicted regeneration. In the malignant group, parenchymal hepatic resection rate (PHRR%) [OR 0.141 (95%CI, 0.040–0.499), P = 0.002] and TBil [OR 3.384 (95%CI, 1.377–8.319), P = 0.008] were independent prognostic factors. ConclusionFLRV%, PHRR%, TBil and INR were predictive factors associated with liver regeneration.

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy.

The success of liver resection relies on the ability of the remnant liver to regenerate. Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies, and data on humans are scarce. Additionally, there is limited knowledge about the preoperative factors that influence postoperative regeneration. To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regeneration. A total of 268 patients who received partial hepatectomy were enrolled. Patients were grouped into right hepatectomy/trisegmentectomy (RH/Tri), left hepatectomy (LH), segmentectomy (Seg), and subsegmentectomy/nonanatomical hepatectomy (Sub/Non) groups. The regeneration index (RI) and late regeneration rate were defined as (postoperative liver volume)/[total functional liver volume (TFLV)] × 100 and (RI at 6-months - RI at 3-months)/RI at 6-months, respectively. The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as "low regeneration" and "delayed regeneration". "Restoration to the original size" was defined as regeneration of the liver volume by more than 90% of the TFLV at 12 months postsurgery. The numbers of patients in the RH/Tri, LH, Seg, and Sub/Non groups were 41, 53, 99 and 75, respectively. The RI plateaued at 3 months in the LH, Seg, and Sub/Non groups, whereas the RI increased until 12 months in the RH/Tri group. According to our multivariate analysis, the preoperative albumin-bilirubin (ALBI) score was an independent factor for low regeneration at 3 months [odds ratio (OR) 95%CI = 2.80 (1.17-6.69), P = 0.02; per 1.0 up] and 12 months [OR = 2.27 (1.01-5.09), P = 0.04; per 1.0 up]. Multivariate analysis revealed that only liver resection percentage [OR = 1.03 (1.00-1.05), P = 0.04] was associated with delayed regeneration. Furthermore, multivariate analysis demonstrated that the preoperative ALBI score [OR = 2.63 (1.00-1.05), P = 0.02; per 1.0 up] and liver resection percentage [OR = 1.02 (1.00-1.05), P = 0.04; per 1.0 up] were found to be independent risk factors associated with volume restoration failure. Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score. This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration

Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure: A systematic review.

Post-hepatectomy liver failure (PHLF) is one of the main causes of postoperative mortality and is challenging to predict early in patients after liver resection. Some studies suggest that the postoperative serum phosphorus might predict outcomes in these patients. To perform a systematic literature review on hypophosphatemia and evaluate it as a prognostic factor for PHLF and overall morbidity. This systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses statement. A study protocol for the review was registered in the International Prospective Register of Systematic Reviews database. PubMed, Cochrane and Lippincott Williams & Wilkins databases were systematically searched up to March 31, 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for PHLF, overall postoperative morbidity and liver regeneration. The quality assessment of the included cohort studies was performed according to the Newcastle-Ottawa Scale. After final assessment, nine studies (eight retrospective and one prospective cohort study) with 1677 patients were included in the systematic review. All selected studies scored ≥ 6 points according to the Newcastle-Ottawa Scale. Cutoff values of hypophosphatemia varied from < 1 mg/dL to ≤ 2.5 mg/dL in selected studies with ≤ 2.5 mg/dL being the most used defining value. Five studies analyzed PHLF, while the remaining four analyzed overall complications as a main outcome associated with hypophosphatemia. Only two of the selected studies analyzed postoperative liver regeneration, with reported better postoperative liver regeneration in cases of postoperative hypophosphatemia. In three studies hypophosphatemia was associated with better postoperative outcomes, while six studies revealed hypophosphatemia as a predictive factor for worse patient outcomes. Changes of the postoperative serum phosphorus level might be useful for predicting outcomes after liver resection. However, routine measurement of perioperative serum phosphorus levels remains questionable and should be evaluated individually.

Transcriptomic landscapes of effective and failed liver regeneration in humans

Although extensive experimental evidence on the process of liver regeneration exists, in humans, validation is largely missing. However, liver regeneration is critically affected by underlying liver disease. Within this project, we aimed to systematically assess early transcriptional changes during liver regeneration in humans and further assess how these processes differ in people with dysfunctional liver regeneration. Blood samples of 154 patients and intraoperative tissue samples of 46 patients undergoing liver resection were collected and classified with regard to dysfunctional postoperative liver regeneration. Of those, a matched cohort of 21 patients were used for RNA sequencing. Samples were assessed for circulating cytokines, gene expression dynamics, intrahepatic neutrophil accumulation, and spatial transcriptomics. Individuals with dysfunctional liver regeneration demonstrated an aggravated transcriptional inflammatory response with higher intracellular adhesion molecule-1 induction. Increased induction of this critical leukocyte adhesion molecule was associated with increased intrahepatic neutrophil accumulation and activation upon induction of liver regeneration in individuals with dysfunctional liver regeneration. Comparing baseline gene expression profiles in individuals with and without dysfunctional liver regeneration, we found that dual-specificity phosphatase 4 (DUSP4) expression, a known critical regulator of intracellular adhesion molecule-1 expression in endothelial cells, was markedly reduced in patients with dysfunctional liver regeneration. Mimicking clinical risk factors for dysfunctional liver regeneration, we found liver sinusoidal endothelial cells of two liver disease models to have significantly reduced baseline levels of DUSP4. Exploring the landscape of early transcriptional changes of human liver regeneration, we observed that people with dysfunctional regeneration experience overwhelming intrahepatic inflammation. Subclinical liver disease might account for DUSP4 reduction in liver sinusoidal endothelial cells, which ultimately primes the liver for an aggravated inflammatory response. Using a unique human biorepository, focused on liver regeneration (LR), we explored the landscape of circulating and tissue-level alterations associated with both functional and dysfunctional LR. In contrast to experimental animal models, people with dysfunctional LR demonstrated an aggravated transcriptional inflammatory response, higher intracellular adhesion molecule-1 (ICAM-1) induction, intrahepatic neutrophil accumulation and activation upon induction of LR. Although inflammatory responses appear rapidly after liver resection, people with dysfunctional LR have exaggerated inflammatory responses that appear to be related to decreased levels of LSEC DUSP4, challenging existing concepts of post-resectional LR.

Ahnak depletion accelerates liver regeneration by modulating the TGF-β/Smad signaling pathway

Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostai-ning, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

Investigation of the Relevance of Platelet Alpha Granules for Postoperative Liver Regeneration in a Mouse Model of Partial Hepatectomy

Introduction: Platelet alpha granule release was previously associated to development of liver dysfunction after liver resection. However, the relevance of platelet degranulation in liver regeneration has not been elucidated thus far. Here we aimed to investigate differences in liver regeneration between mice lacking alpha granules and wild type individuals after partial hepatectomy (pHx).

The Ratio of Activin A and FLRG Allows Prediction of Postoperative Liver Dysfunction in Patients Undergoing Liver Resection

Introduction: Postoperative liver dysfunction (LD) remains a life-threatening complication after liver resection. With no causal therapy available, research focusing on understanding postoperative liver regeneration (LR) and the prediction of postoperative LD is of importance. Here, we evaluate the predictive potential for postoperative LD of activin A and its inhibitory protein FLRG and assess their influence on the development of LD. Method: Activin A and FLRG were evaluated in plasma of 59 patients undergoing liver resection using commercially available ELISA kits. Plasma was prepared from blood taken prior to the operation (preOP), as well as on the first and fifth postoperative day (POD). Postoperative outcome was prospectively documented. Results: When evaluating the perioperative dynamic of activin A and FLRG, we observed a significant decrease in plasma for both parameters on POD1 (p=0.045 and p=0.005, respectively). FLRG showed an increase from POD1 on POD5 (p=0.004). Interestingly, neither activin A nor FLRG were different between patients with and without postoperative LD at any timepoint. However, the ratio activin A / FLRG was significantly higher in patients without LD prior to liver resection (p=0.037). There was no perioperative dynamic for activin A / FLRG. Conclusions: While the circulating dynamics of activin A and FLRG showed no association with LD, the ratio of activin A / FLRG was significantly decreased in patients developing postoperative LD prior to liver resection. While the pathophysiology behind these findings still warrants further research, activin A shows potential as a possible predictor of postoperative LD.

Predictive implication for liver regeneration by transient elastography in patients with major hepatectomy of perihilar cholangiocarcinoma

There are many studies regarding postoperative liver regeneration after major hepatectomy related to posthepatectomy liver failure (PHLF). However, there are no study which focused on liver fibrosis measured by transient elastography and liver regeneration. Therefore, we aimed to evaluate the correlation between transient elastography and liver regeneration in patients who underwent surgery for perihilar cholangiocarcinoma (PHCC). Patients who underwent major hepatectomy for PHCC with curative intent between 2016 and 2020 were included in the study. Patients were divided into groups by the value of liver stiffness measured by transient liver elastography and the cutoff values for severity of fibrosis were derived from the study by Tsochatzis et al. Liver volumes were compared between preoperative and postoperative day 5 CT scan. Of the 45 patients who underwent surgery for PHCC, F1 group was consisted of 23 (51.1%) patients, F2 group 10 (22.2%), F3 group 9 (20.0%), and F4 group 3 (6.7%) patients. The patients were divided into 2 groups, F1 and F2 as Group A and F3 and F4 as Group B. The ICG R 15 value was 14.7 ± 6.6 in Group A and 20.3 ± 9.9 in Group B (p = 0.034). The mean value of liver volume increase rate of each group was 42.3% ± 30.9% in Group A, and 37.4% ± 24.6% in Group B (p = 0.622). This study suggests that liver fibrosis has a tendency to be related with less liver regeneration but without clinical significance. However, transient elastography could be used as one of the useful predictor reference for liver regeneration related to PHLF.

Splenic Enlargement Induced by Preoperative Chemotherapy Is an Useful Indicator for Predicting Liver Regeneration after Resection for Colorectal Liver Metastases

Introduction: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. Methods: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty one patients had conversion chemotherapy. The other 67 patients underwent upfront liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. Results: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. Conclusion: Splenic enlargement induced by preoperative chemotherapy was a useful evaluation indicator for impaired liver regeneration after resection and a decision-making tool for treatment strategy for unresectable CRLMs.

Importance of Platelet - Endothelial Cell Interaction during Postoperative Liver Regeneration

Introduction: Interleukin-6 (IL-6) is a well-known regulator of liver regeneration, specifically during the early period. Within this project, we wanted to identify the time course of IL-6 production within the human liver during the early phase of liver regeneration as a result of the potential interaction of platelets and liver sinusoidal endothelial cells (LSECs).

Postoperative liver regeneration does not elicit recurrence of colorectal cancer liver metastases after major hepatectomy

Background and objectivesRecurrence is a frequent concern in curatively resected CRC liver metastases. Translational research suggests that regeneration upon hepatectomy may also alleviate metastatic recurrence; however, the significance in patients is unclear. We therefore sought to study the effect of liver regeneration on tumor recurrence in patients. MethodsIn this retrospective cohort study, we included 58 out of 186 potentially eligible patients from our prospectively maintained database of CRC liver metastasis patients between 2001 and 2012 with a median follow-up of 42 months who underwent a formal right or left hemihepatectomy. Liver regeneration in CT volumetry was correlated with recurrence of CRC liver metastases and overall survival. ResultsLiver regeneration increased up to 14 months to 21.0% for left and 122.6% for right hemihepatectomy, respectively, with comparable final volumes. Regeneration was independent of initial tumor stage, number of metastases, and preoperative chemotherapy. Patients with lower liver regeneration showed earlier recurrence of CRC liver metastases (p = 0.006). Overall survival did not differ in patients with weak versus strong liver regeneration. ConclusionsThe extent of liver regeneration after major hepatectomy does not impede overall survival. Therefore, our data encourage aggressive therapeutical regimes for CRC liver metastases involving major hepatectomies as part of a curative approach.

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases

BackgroundConversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection.MethodsWe retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed.ResultsA ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration.ConclusionsSplenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

PP2Acα inhibits PFKFB2-induced glycolysis to promote termination of liver regeneration

The mechanisms underlying the initiation and proliferation of liver regeneration (LR) has been extensively studied using the partial hepatectomy (PHx) model, while little is known about the termination of LR. PP2Acα (protein phosphatase 2 A catalytic subunit α isoform) is the catalytic subunit of protein phosphatase 2 A (PP2A), accounting for most of intracellular serine/threonine phosphatase activity. We have previously observed that termination of LR delayed in PP2Acα liver-specific knockout (LKO) mice after PHx. In our study, we used phospho explorer antibody array analysis to screen the potential phosphorylation targets of PP2Acα, and PP2Acα had a great influence on the hepatic phosphoproteomic signaling in the termination of LR after PHx. We then tested the phosphorylation changes and metabolic function of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2 (PFKFB2), an isoform of the key glycolytic enzyme PFKFB, which was significantly regulated by PP2Acα knockout. PP2Acα knockout enhanced glycolysis in vivo and in vitro, while adenoviral-mediated RNAi of PFKFB2 reversed the extension of postoperative liver regeneration in KO mice along with the downregulation of glycolysis. Therefore, we demonstrated that PP2Acα liver-specific knockout regulated the hepatocytes glycolysis via activating PFKFB2, thus enhancing liver regeneration during the termination stage.

Perioperative use of selective serotonin reuptake inhibitors is associated to poor postoperative outcome in patients undergoing liver resection

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Recently, modification of intra-platelet serotonin levels as therapeutic intervention to promote postoperative liver regeneration was proposed. In this context, we previously showed a bivalent effect of serotonin on liver regeneration and early tumour recurrence. We were able to provide exploratory data on the use of selective serotonin reuptake inhibitors (SSRI) within the previous publications. Yet, this data has to be considered exploratory, as the number of patients under SSRI treatment was extremely low. Accordingly, we aimed to evaluate the use of selective serotonin reuptake inhibitors (SSRI) in a large cohort of patients undergoing liver resection. Methods: In total, 755 patients undergoing liver resection were retrospectively included from our prospectively maintained institutional database. Perioperative intake of SSRI was evaluated and patients were followed up for postoperative liver dysfunction (LD) and morbidity. Results: Within this cohort 75 patients (9.9%) with perioperative SSRI therapy could be identified. Of note, patients treated with SSRI showed a higher incidence of severe morbidity (22.9% - no SSRI vs 31.6% - SSRI, p<0.05) and a significantly increased incidence of liver dysfunction (10.7% - no SSRI vs 23.4% - SSRI, p<0.05). On the other hand, patients receiving SSRI therapy were found to suffer from significantly reduced early tumor recurrences at 6 and 12 months after surgery (6 months: 13.0% - no SSRI vs 22.7% - SSRI, p<0.05; 12 months: 26.3% - no SSRI vs 42.1% - SSRI, p<0.05). Conclusion: Within the present study we present solid data on the influence of SSRI on postoperative clinical outcome. Indeed, perioperative SSRI treatment seems to be associated to development of LD most likely via downregulation of intra-platelet serotonin, which was shown to be central for postoperative liver regeneration. However, SSRI therapy also seems to supressearly tumor recurrences and might therefore reflect an attractive adjuvant therapy in patients after liver resection.

The role of imaging in surgical planning for liver resection: what the radiologist need to know.

The management of patients undergoing surgical resection for liver malignancies requires a multidisciplinary team, including a dedicated radiologist. In the preoperative workup, the radiologist has to provide precise, relevant information to the surgeon. This requires the radiologist to know the basics of surgical techniques as well as liver surgical anatomy in order to help to avoid unexpected surgical scenarios and complications. Moreover, virtual resections and volumetries on radiological images will be discussed, and basic concepts of postoperative liver failure, regeneration, and methods for hypertrophy induction will be provided. (www.actabiomedica.it)

Liver regeneration after resection in clinical and experimental conditions

The researches devoted to postoperative liver regeneration and influence in this process were analyzed. Liver injury is followed by hypertrophy of residual liver parenchyma. The use of various cytokines is perspective for activation, acceleration and inhibition of liver recovery. Cellular technologies in the treatment of liver diseases can affect its repair. Moreover, these methods could make unnecessary resection and transplantation of liver in certain cases. It is generally accepted that the main effect of multipotent stromal cells (MSC) in liver failure is associated with their differentiation to the cellular elements of this organ. At the same time, recent reports revealed that MSC injection to the liver is followed by their quick death, dissemination to other organs and tissues or even elimination from the organism. Regeneration of non-parenchymal structures (vascular network and bile ducts) should be considered in addition to functional recovery of liver parenchyma after resection. Clarification of indications and contraindications for MSC therapy, as well as prevention of possible complications associated with cellular technologies are required.

Functional and volumetric assessment of postoperative liver regeneration after major liver resection

Functional and volumetric assessment of postoperative liver regeneration after major liver resection

Hallmarks of postoperative liver regeneration: An updated insight on the regulatory mechanisms.

Performance and advances in liver surgery makes remarkable progress of the understanding of liver regeneration. Liver regeneration after liver resection has been widely researched, and the underlying mechanism mostly concerns proliferation of hepatocytes and the influence by inflammation through activation of Kupffer cells and the other parenchymal cells, the second regenerative pathway by hepatic progenitor cells (HPCs), inducing angiogenesis, remodeling of a extracellular matrix (ECM), and termination mechanisms. New clinical surgeries and the updated multiomics analysis are exploiting the remarkable progress, especially in immune regulation and metabolic process of two emerging hallmarks. This review briefly represents a systemic outline of eight hallmarks, including hepatocyte proliferation, contribution of hepatic progenitor cells, inducing angiogenesis, reprogramming of the extracellular matrix, apoptosis and termination of proliferation, inflammation, immune and metabolic regulation, which are set as organizing characteristics of postoperative liver regeneration and future directions of refining treatment targets.