Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial.

BACKGROUND: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).

Minimally Invasive Donor Hepatectomy for Adult Living Donor Liver Transplantation: An International, Multi-institutional Evaluation of Safety, Efficacy and Early Outcomes.

OBJECTIVE: Evaluating the perioperative outcomes of minimally invasive (MIV) donor hepatectomy for adult live donor liver transplants in a large multi-institutional series from both Eastern and Western centers. BACKGROUND: Laparoscopic liver resection has become standard practice for minor resections in selected patients in whom it provides reduced postoperative morbidity and faster rehabilitation. Laparoscopic approaches in living donor hepatectomy for transplantation, however, remain controversial because of safety concerns. Following the recommendation of the Jury of the Morioka consensus conference to address this, a retrospective study was designed to assess the early postoperative outcomes after laparoscopic donor hepatectomy. The collective experience of 10 mature transplant teams from Eastern and Western countries was reviewed. METHODS: All centers provided data from prospectively maintained databases. Only left and right hepatectomies performed using a MIV technique were included in this study. Primary outcome was the occurrence of complications using the Clavien-Dindo graded classification and the Comprehensive Complication Index during the first 3 months. Logistic regression analysis was used to identify risk factors for complications. RESULTS: In all, 412 MIV donor hepatectomies were recorded including 164 left and 248 right hepatectomies. Surgical technique was either pure laparoscopy in 175 cases or hybrid approach in 237. Conversion into standard laparotomy was necessary in 17 donors (4.1%). None of the donors died. Also, 108 experienced 121 complications including 9.4% of severe (Clavien-Dindo 3-4) complications. Median Comprehensive Complication Index was 5.2. CONCLUSIONS: This study shows favorable early postoperative outcomes in more than 400 MIV donor hepatectomy from 10 experienced centers. These results are comparable to those of benchmarking series of open standard donor hepatectomy.

Risk Factors of Positive Resection Margin in Laparoscopic and Open Liver Surgery for Colorectal Liver Metastases: A New Perspective in the Perioperative Assessment: A European Multicenter Study.

OBJECTIVE: To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs. BACKGROUND: The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet. METHODS: A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed. RESULTS: Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665-0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671-0.745). CONCLUSIONS: The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS.

90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial.

Background Transarterial chemoembolization (TACE) is the recommended treatment for intermediate hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer guidelines. Prospective uncontrolled studies suggest that yttrium 90 (90Y) transarterial radioembolization (TARE) is a safe and effective alternative. Purpose To compare the efficacy and safety of TARE with TACE for unresectable HCC. Materials and Methods In this single-center prospective randomized controlled trial (TRACE), 90Y glass TARE was compared with doxorubicin drug-eluting bead (DEB) TACE in participants with intermediate-stage HCC, extended to Eastern Cooperative Oncology Group performance status 1 and those with early-stage HCC not eligible for surgery or thermoablation. Participants were recruited between September 2011 and March 2018. The primary end point was time to overall tumor progression (TTP) (Kaplan-Meier analysis) in the intention-to-treat (ITT) and per-protocol (PP) groups. Results At interim analysis, 38 participants (median age, 67 years; IQR, 63-72 years; 33 men) were randomized to the TARE arm and 34 (median age, 68 years; IQR, 61-71 years; 30 men) to the DEB-TACE arm (ITT group). Median TTP was 17.1 months in the TARE arm versus 9.5 months in the DEB-TACE arm (ITT group hazard ratio [HR], 0.36; 95% CI: 0.18, 0.70; P = .002) (PP group, 32 and 34 participants, respectively, in each arm; HR, 0.29; 95% CI: 0.14, 0.60; P < .001). Median overall survival was 30.2 months after TARE and 15.6 months after DEB-TACE (ITT group HR, 0.48; 95% CI: 0.28, 0.82; P = .006). Serious adverse events grade 3 or higher (13 of 33 participants [39%] vs 19 of 36 [53%] after TARE and DEB-TACE, respectively; P = .47) and 30-day mortality (0 of 33 participants [0%] vs three of 36 [8.3%]; P = .24) were similar in the safety groups. At the interim, the HR for the primary end point, TTP, was less than 0.39, meeting the criteria to halt the study. Conclusion With similar safety profile, yttrium 90 radioembolization conferred superior tumor control and survival compared with chemoembolization using drug-eluting beads in selected participants with early or intermediate hepatocellular carcinoma. Clinical trial registration no. NCT01381211 © RSNA, 2022 Online supplemental material is available for this article.

Outcome of primary ERCP versus primary PTC for biliary drainage in malignant hilar biliary strictures: a systematic review and meta-analysis.

BACKGROUND: Patients with malignant hilar biliary strictures can suffer from obstructive jaundice. Controversy remains on the optimal approach to obtain preoperative or palliative biliary drainage in these patients. A systematic review and meta-analysis was conducted to compare the two modalities most commonly used in this scenario: endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). METHODS: MEDLINE via PubMed was searched for relevant articles published from 2005 to April 2019. Following outcome measures were used to compare ERCP and PTC: therapeutic success rate, cholangitis, pancreatitis, bleeding, tube dislocation, reintervention rate, mortality such as 30d mortality and in-hospital death, median survival time, drainage patency, duration until decompression and hospital stay. Risk of bias assessment for the retrospective studies was conducted by NOS. RoB 2 was used for RCT. A meta-analysis was performed by using Review Manager 5.3. The certainty of evidence was appraised using GRADE. RESULTS: Eleven articles of which one RCT and ten retrospective cohort studies fulfilled the inclusion criteria for data-analysis (1417 patients; 784 ERCP, 633 PTC). The combined odds ratio (OR) for therapeutic succes was 3.5 times higher in the PTC group (95% CI 2.05-5.97; high certainty). In terms of cholangitis, ERCP carried a 1.7-fold risk as compared to PTC (95% CI 0.92-3.08; moderate certainty). Patients who underwent ERCP were 11.50 times more likely to undergo a reintervention (95% CI 3.51-37.70; moderate certainty). ERCP was comparable to PTC in terms of pancreatitis (low certainty), bleeding (high certainty) and tube dislocation rate (moderate certainty). Mortality tended to be numerically higher in the PTC group but low patient numbers, selection bias and study heterogeneity did not allow uniform comparative analysis. CONCLUSIONS: In patients with malignant hilar biliary strictures, PTC is associated with a better therapeutic success rate, less cholangitis and lower reintervention rate as compared to ERCP.

Performance with robotic surgery versus 3D- and 2D-laparoscopy during pancreatic and biliary anastomoses in a biotissue model: pooled analysis of two randomized trials.

BACKGROUND: Robotic surgery may improve surgical performance during minimally invasive pancreatoduodenectomy as compared to 3D- and 2D-laparoscopy but comparative studies are lacking. This study assessed the impact of robotic surgery versus 3D- and 2D-laparoscopy on surgical performance and operative time using a standardized biotissue model for pancreatico- and hepatico-jejunostomy using pooled data from two randomized controlled crossover trials (RCTs). METHODS: Pooled analysis of data from two RCTs with 60 participants (36 surgeons, 24 residents) from 11 countries (December 2017-July 2019) was conducted. Each included participant completed two pancreatico- and two hepatico-jejunostomies in biotissue using 3D-robotic surgery, 3D-laparoscopy, or 2D-laparoscopy. Primary outcomes were the objective structured assessment of technical skills (OSATS: 12-60) rating, scored by observers blinded for 3D/2D and the operative time required to complete both anastomoses. Sensitivity analysis excluded participants with excess experience compared to others. RESULTS: A total of 220 anastomoses were completed (robotic 80, 3D-laparoscopy 70, 2D-laparoscopy 70). Participants in the robotic group had less surgical experience [median 1 (0-2) versus 6 years (4-12), p < 0.001], as compared to the laparoscopic group. Robotic surgery resulted in higher OSATS ratings (50, 43, 39 points, p = .021 and p < .001) and shorter operative time (56.5, 65.0, 81.5 min, p = .055 and p < .001), as compared to 3D- and 2D-laparoscopy, respectively, which remained in the sensitivity analysis. CONCLUSION: In a pooled analysis of two RCTs in a biotissue model, robotic surgery resulted in better surgical performance scores and shorter operative time for biotissue pancreatic and biliary anastomoses, as compared to 3D- and 2D-laparoscopy.

Illness cognitions and health-related quality of life in liver transplant patients related to length of stay, comorbidities and complications.

PURPOSE: Illness cognitions regarding helplessness and acceptance are known to play a role in health-related quality of life (HRQoL). Our study examined the evolution of these illness cognitions and the physical (PQoL) and mental QoL (MQoL) in liver transplantation (LT) patients over time in relation to pre- and postoperative clinical factors. METHODS: We performed an analytical cross-sectional study using self-report questionnaires at 4 timeframes: preLT, postLT0-3 m, postLT1y, and postLT2y. T-test was used to identify the influence of different clinical factors related to the LT on postLT2y QoL and illness cognition. Linear mixed models were used to determine evolution. RESULTS: PostLT patients showed significant less helplessness and more acceptance cognitions. PQoL and MQoL decreased postLT0-3 m, then started to increase and are highest at postLT1y. Patients with preLT ascites showed significantly less helplessness postLT2y, while patients with a low preLT MELD score < 20 showed a significant better MQoL postLT2y. Biliary complications and re-transplantation were associated with more helplessness and a worse PQoL postLT1y-2y. Length of stay in ICU and hospital was negatively correlated with illness cognitions and PQoL and MQoL postLT1y. CONCLUSIONS: Our findings confirm that liver transplant patients have improvement of illness cognitions and mental and physical HRQoL at 1 and 2 years after liver transplantation. A postoperative period without complications and with short stay in ICU and in hospital, is important to achieve PQoL and feeling less helpless, while the MQoL is influenced by acceptance and preLT PQoL. Multidisciplinary approach preLT and postLT should be standard care.

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation.

OBJECTIVES: Autoantibodies (AAb) and donor-specific HLA antibodies (DSA) are frequently present in pediatric liver transplant (LT) recipients. Their clinical significance remains incompletely understood. We aimed to investigate the prevalence of serum AAb and DSA in pediatric LT recipients and its correlation with patient characteristics and histological and biochemical parameters. METHODS: We retrospectively reviewed the data from 62 pediatric LT patients in follow-up at Ghent University Hospital between January 2007 and February 2018. Blood samples with AAb measurement were taken systematically, liver biopsies (LB) were performed on clinical indication. RESULTS: AAb were detected in 27 (43.3%) patients, with antinuclear antibodies (ANA) being the most frequently (24%) encountered AAb. There was an association between AAb positivity and female gender (P = 0,032) and deceased donor LT (P = 0,006). Patients with positive AAb underwent a higher number of LB during their follow-up (P < 0,001), and an association was found with the presence of nonspecific histologic alterations (P = 0,032) in the absence of de novo autoimmune hepatitis. Positive AAb were also associated with higher alkaline phosphatase (P < 0,001), ALT (P < 0,001), AST (P < 0,001), γ-GT (P = 0,001), IgG (P = 0,011) and lower albumin (P = 0,029). Fourteen out of 50 (28%) patients were DSA-positive, mostly anti-HLA class II. DSA positivity was associated with T-cell-mediated rejection (P = 0,019), higher total (P = 0,033), and direct (P = 0,012) bilirubin and γ-GT (P < 0,001). CONCLUSIONS: The presence of AAb and DSA is associated with histological and biochemical parameters of graft dysfunction. Larger prospective studies are warranted to investigate the causal relationships between AAb and DSA development and outcome parameters post pediatric LT.

Added value of 3D-vision during robotic pancreatoduodenectomy anastomoses in biotissue (LAEBOT 3D2D): a randomized controlled cross-over trial.

BACKGROUND: We tested the added value of 3D-vision on procedure time and surgical performance during robotic pancreatoduodenectomy anastomoses in biotissue. Robotic surgery has the advantage of articulating instruments and 3D-vision. Consensus is lacking on the added value of 3D-vision during laparoscopic surgery. Given the improved dexterity with robotic surgery, the added value of 3D-vision may be even less with robotic surgery. METHODS: In this experimental randomized controlled cross-over trial, 20 surgeons and surgical residents from 5 countries performed robotic pancreaticojejunostomy and hepaticojejunostomy anastomoses in a biotissue organ model using the da Vinci® system and were randomized to start with either 3D- or 2D-vision. Primary endpoint was the time required to complete both anastomoses. Secondary endpoint was the objective structured assessment of technical skill (OSATS; range 12-60) rating; scored by two observers blinded to 3D/2D. RESULTS: Robotic 3D-vision reduced the combined operative time from 78.1 to 57.3 min (24.6% reduction, p < 0.001; 20.8 min reduction, 95% confidence intervals 12.8-28.8 min). This reduction was consistent for both anastomoses and between surgeons and residents, p < 0.001. Robotic 3D-vision improved OSATS performance by 6.1 points (20.8% improvement, p = 0.003) compared to 2D (39.4 to 45.1 points, ± 5.5). CONCLUSION: 3D-vision has a considerable added value during robotic pancreatoduodenectomy anastomoses in biotissue in both time reduction and improved surgical performance as compared to 2D-vision.

Prophylactic Mesh After Midline Laparotomy: Evidence is out There, but why do Surgeons Hesitate?

BACKGROUND: Incisional hernias have an impact on patients' quality of life and on health care finances. Because of high recurrence rates despite mesh repair, the prevention of incisional hernias with prophylactic mesh reinforcement is currently a topic of interest. But only 15% of surgeons are implementing it, mainly because of fear for mesh complications and disbelief in the benefits. The goal of this systematic review is to evaluate the effectiveness and safety of prophylactic mesh in adult patients after midline laparotomy. METHODS: An extensive literature search was performed in PubMed, Embase and CENTRAL until 9/5/2020 for RCTs and cohort studies regarding mesh reinforcement versus primary suture closure of a midline laparotomy. The quality of the articles was analyzed using the Scottish Intercollegiate Guidelines Network checklists. Revman 5 was used to perform a meta-analysis. RESULTS: Twenty-three articles were found with a total of 1633 patients in the mesh reinforcement group and 1533 in the primary suture group. An odds ratio for incisional hernia incidence of 0.37 (95% CI = [0.30, 0.46], p < 0.01) with RCTs and of 0.15 (95% CI = [0.09,0.25], p < 0.01) in cohort studies was calculated. Seroma rate shows a significant odds ratio of 2.18 (95% CI = [1.45, 3.29], p < 0.01) in favor of primary suture. No increase was found regarding other complications. CONCLUSION: The evidence for the use of prophylactic mesh reinforcement is overwhelming with a significant reduction in incisional hernia rate, but implementation in daily clinical practice remains limited. Instead of putting patients at risk for incisional hernia formation and subsequent complications, surgeons should question their arguments why not to use mesh reinforcement, specifically in high-risk patients.

Local control of hepatocellular carcinoma and colorectal liver metastases after surgical microwave ablation without concomitant hepatectomy.

PURPOSE: Microwave ablation (MWA) is an accepted technique in the multimodal treatment of hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Study endpoints were to evaluate the local efficacy of surgical MWA in selected patients with oligonodular disease without the combination of liver resection to allow a clear interpretation of the follow-up imaging and compare it to the results on percutaneous MWA available in the literature. METHODS: Consecutive MWA-only procedures performed between May 2013 and May 2018 for HCC and CRLM with free-hand ultrasound guidance were identified. MWA systems with 2450 MHz were used. Incomplete ablation (IA) was defined as residual disease within 1 cm of the ablation site at the first post-ablation imaging and local recurrence (LR) as the presence of disease after at least one tumor-free imaging. RESULTS: A total of 70 tumors in 47 patients were treated with 46 laparoscopic and 1 open procedures. Each patient had no more than 3 tumors, and median size of the lesions was 15 mm (IQR: 10-22). After a median follow-up of 26 months (IQR: 12-40), IA rate was 8.6% and LR rate was 29.4%. Multivariable analysis showed that vascular proximity (OR = 3.4; 95% CI = 1.26-9.22; p=0.016) was the only significant predictor of the combined outcome IA or LR. DISCUSSION: In the present study, after mostly laparoscopic MWA, LR was higher than the rates available in the literature for percutaneous MWA of HCC but lower than in the limited studies analyzing isolated percutaneous MWA of liver metastases. Future developments may help establish the role of each therapeutic modality per tumor, in order to improve the outcomes.

Laparoscopic Versus Open Thermal Ablation of Colorectal Liver Metastases: A Propensity Score-Based Analysis of Local Control of the Ablated Tumors.

BACKGROUND: Laparoscopic ablation (LA) of colorectal liver metastases (CRLMs) is frequently performed in combination with laparoscopic liver resection or as a stand-alone procedure. However, LA is technically demanding and whether the results are comparable with those of open ablation (OA) has not been determined to date. This study compared the effectiveness of LA and OA in achieving local tumor control of CRLMs. METHODS: Patients undergoing LA or OA of CRLMs at Ghent University Hospital between June 2007 and February 2018 were identified from a prospective database. Lesions treated by LA and OA were matched 1:1 using a propensity score based on lesions (liver segment, size, deepness, proximity to a vessel), patients, and procedural characteristics. Ablation sites were followed up with computed-tomography or magnetic resonance imaging to assess the completeness of the ablation and ablation-site recurrence (ASR). Analysis of ASR was performed with the Kaplan-Meier method and Cox regression. RESULTS: In this study, 163 patients underwent the surgical ablation (78 LA, 85 OA) of 333 CRLMs (143 LA, 190 OA). After matching, 220 lesions (110 LA, 110 OA) were analyzed. Ablation was complete in 93.7% (LA) and 97.3% (OA) of the sites (p = 0.195). No difference in ASR was observed (p = 0.351), with a cumulative risk of ASR at 12 months of 9.1% (LA) and 8.2% (OA). After multivariable analysis, ASR was confirmed to be independent of the surgical approach. CONCLUSION: The findings showed that LA and OA achieve a comparable local control of CRLMs. This result further supports the adoption of a laparoscopic approach for the treatment of CRLMs.

Up to 50% of portal vein thrombosis remains undiagnosed until liver transplantation.

BACKGROUND: Impact of portal vein thrombosis (PVT) on the clinical course in liver transplant candidates remains unclear. This study aims to identify prevalence and risk factors for PVT, assess outcome after liver transplantation (LT) in patients with PVT and study the effect of anticoagulation. METHODS: This single-center retrospective cohort study was performed from January 2006 until June 2016. Patients were stratified according to presence of PVT. Risk factors and outcome were assessed using logistic regression and survival analysis. RESULTS: Among 390 adults who underwent orthotopic LT, PVT occurred in 40 (10.3%). In, respectively, 10 (25%), 7 (17.5%), and 23 (57.5%) patients, PVT was identified at time of evaluation for transplantation, on the waiting list and during transplantation. A beneficial trend was present favoring the use of anticoagulation for PVT resolution (n = 3/7 vs 0/9; p = .062). Patient and graft survival were similar between the groups after a median follow-up of 5 years. However, 1-year patient survival was significantly lower (p = .031) in patients with PVT. CONCLUSION: Portal vein thrombosis occurred in 10% of patients awaiting LT was undiagnosed in 50% until moment of LT and had a deleterious effect on 1-year survival. Anticoagulation showed a beneficial trend on recanalization of PVT and survival rate.

Long-Term and Oncologic Outcomes of Robotic Versus Laparoscopic Liver Resection for Metastatic Colorectal Cancer: A Multicenter, Propensity Score Matching Analysis.

BACKGROUND: To assess long-term oncologic outcomes of robotic-assisted liver resection (RLR) for colorectal cancer (CRC) metastases as compared to a propensity-matched cohort of laparoscopic liver resections (LLR). Although safety and short-term outcomes of RLR have been described and previously compared to LLR, long-term and oncologic data are lacking. METHODS: A retrospective study was performed of all patients who underwent RLR and LLR for CRC metastases at six high-volume centers in the USA and Europe between 2002 and 2017. Propensity matching was used to match baseline characteristics between the two groups. Data were analyzed with a focus on postoperative and oncologic outcomes, as well as long-term recurrence and survival. RESULTS: RLR was performed in 115 patients, and 514 patients underwent LLR. Following propensity matching 115 patients in each cohort were compared. Perioperative outcomes including mortality, morbidity, reoperation, readmission, intensive care requirement, length-of-stay and margin status were not statistically different. Both prematching and postmatching analyses demonstrated similar overall survival (OS) and disease-free survival (DFS) between RLR and LLR at 5 years (61 vs. 60% OS, p = 0.87, and 38 vs. 31% DFS, p = 0.25, prematching; 61 vs. 60% OS, p = 0.78, and 38 vs. 44% DFS, p = 0.62, postmatching). CONCLUSIONS: Propensity score matching with a large, multicenter database demonstrates that RLR for colorectal metastases is feasible and safe, with perioperative and long-term oncologic outcomes and survival that are largely comparable to LLR.

Effects of propofol and sevoflurane on hepatic blood flow: a randomized controlled trial.

BACKGROUND: Maintaining adequate perioperative hepatic blood flow (HBF) supply is essential for preservation of postoperative normal liver function. Propofol and sevoflurane affect arterial and portal HBF. Previous studies have suggested that propofol increases total HBF, primarily by increasing portal HBF, while sevoflurane has only minimal effect on total HBF. Primary objective was to compare the effect of propofol (group P) and sevoflurane (group S) on arterial, portal and total HBF and on the caval and portal vein pressure during major abdominal surgery. The study was performed in patients undergoing pancreaticoduodenectomy because - in contrast to hepatic surgical procedures - this is a standardized surgical procedure without potential anticipated severe hemodynamic disturbances, and it allows direct access to the hepatic blood vessels. METHODS: Patients were randomized according to the type of anesthetic drug used. For both groups, Bispectral Index (BIS) monitoring was used to monitor depth of anesthesia. All patients received goal-directed hemodynamic therapy (GDHT) guided by the transpulmonary thermodilution technique. Hemodynamic data were measured, recorded and guided by Pulsioflex™. Arterial, portal and total HBF were measured directly, using ultrasound transit time flow measurements (TTFM) and were related to hemodynamic variables. RESULTS: Eighteen patients were included. There was no significant difference between groups in arterial, portal and total HBF. As a result of the GDHT, pre-set hemodynamic targets were obtained in both groups, but MAP was significantly lower in group S (p = 0.01). In order to obtain these pre-set hemodynamic targets, group S necessitated a significantly higher need for vasopressor support (p < 0.01). CONCLUSION: Hepatic blood flow was similar under a propofol-based and a sevoflurane-based anesthetic regimen. Related to the application of GDHT, pre-set hemodynamic goals were maintained in both groups, but sevoflurane-anaesthetized patients had a significantly higher need for vasopressor support. TRIAL REGISTRATION: Study protocol number is AGO/2017/002 - EC/2017/0164. EudraCT number is 2017-000071-90. Clin.trail.gov, NCT03772106 , Registered 4/12/2018, retrospective registered.

Incisional lumbar hernia after the use of a lumbar artery perforator flap for breast reconstruction.

Autologous breast reconstruction with a perforator flap has become increasingly popular. The free lumbar artery perforator (LAP) flap has been described as a good alternative for autologous breast reconstruction. The LAP flap is a perforator flap based on a single pedicle. This flap is easy to harvest, with minimal donor-site morbidity. We present a case of a lumbar incisional hernia after LAP flap breast reconstruction in a 53-year-old patient. The patient had been treated with a bilateral mastectomy for cancer. Secondary breast reconstruction was performed with a bilateral DIEP flap. Reoperation was necessary because of a failed DIEP flap at the left side. Reconstruction was performed with a free LAP flap. The patient was referred for a right lumbar incisional hernia at the donor-site of the LAP flap. Open repair was performed with a retroperitoneal mesh. The thoracolumbar fascia was closed in with a running suture. Lumbar artery perforator is a perforator flap based on a single pedicle. Although it does not sacrifice any muscle and seems to be associated with minimal donor-site morbidity, we present the first report of a lumbar incisional hernia repair after LAP flap breast reconstruction treated using an open retroperitoneal mesh repair.

Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial.

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 µg), followed by a 2.5 mL/h infusion (somatostatin: 250 µg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

Glycome Patterns of Perfusate in Livers Before Transplantation Associate With Primary Nonfunction.

BACKGROUND & AIMS: Primary nonfunction (PNF) is a rare complication after liver transplantation that requires urgent retransplantation. PNF is associated with livers from extended criteria donors. Clinical and biochemical factors have not been identified that reliably associate with graft function after liver transplantation. Serum patterns of N-glycans associate with changes in the liver. We analyzed perfusate from grafted liver to identify protein glycosylation patterns associated with PNF. METHODS: We performed a prospective study of consecutive patients who underwent liver transplantation (66 patients, from 1 center, in the derivation set, and 56 patients, from 2 centers, in the validation set) in Belgium, from October 1, 2011, through April 30, 2017. All donor grafts were transported using cold static storage, and perfusate samples were collected from the livers by flushing of hepatic veins before transplantation. Protein-linked N-glycans were isolated from perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer. We compared glycan patterns between patients with vs without PNF of transplanted livers. PNF was defined as the need for urgent retransplantation when a graft had no evidence of function, after exclusion of other causes, such as hepatic artery thrombosis or acute cellular rejection. RESULTS: The relative abundance of a single glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan (NGA2F) was significantly increased in perfusate of livers given to 4 patients who developed PNF after liver transplantation compared with livers given to patients who did not develop PNF. Level of NGA2F identified patients with PNF with 100% accuracy. This glycomarker was the only factor associated with PNF in multivariate analysis in the derivation and the validation sets (P < .0001). CONCLUSIONS: In an analysis of patients who underwent liver transplantation, we associated graft perfusate level of glycan NGA2F present on perfusate proteins with development of PNF with 100% accuracy, and validated this finding in a separate cohort of patients. This biomarker might be used to assess grafts before transplantation, especially when high-risk organs are under consideration.

Endoscopic management of biliary leaks: a systematic review with meta-analysis.

BACKGROUND: The first-line approach to the treatment of biliary leaks is endoscopic retrograde cholangiopancreatography. A variety of techniques can be used, including sphincterotomy, stenting, a combination of both techniques, or nasobiliary drainage. We performed a systematic review with meta-analysis to define the optimal strategy. METHODS: We searched MEDLINE/PubMed, EMBASE, CENTRAL, Scopus, Google Scholar, and Web of Science until January 2018 for randomized clinical trials, case-control studies, and prospective cohort studies. Data on procedure, success, and complication rate were extracted. Risk of bias was assessed. A network meta-analysis was performed to compare sphincterotomy alone vs. stenting alone vs. combination treatment. Stenting was further stratified into leak-bridging and short stenting. RESULTS: 11 studies out of 5085 references were included. Compared with sphincterotomy alone, the combination of sphincterotomy with leak-bridging stenting had the highest success rate (risk ratio [RR] 1.15, 95 % confidence interval [CI] 0.97 - 1.50), followed by leak-bridging stenting alone (RR 1.10, 95 %CI 0.84 - 1.44). For nonbridgeable leaks, stenting alone had a higher success rate than sphincterotomy alone (RR 1.07, 95 %CI 0.72 - 1.40). The combination of short stents with sphincterotomy had no added benefit (RR 0.94, 95 %CI 0.49 - 1.29). Overall quality of the included studies was considered to be moderate. CONCLUSIONS: We recommend sphincterotomy with stenting if the biliary leak can be bridged. If not, stenting alone with a short stent may be preferred in order to avoid sphincterotomy-related complications. More and larger studies are needed to confirm these findings.