Successful Thrombectomy via a Surgically Reopened Umbilical Vein for Extended Portal Vein Thrombosis Caused by Portal Vein Embolization prior to Extended Liver Resection

Selective portal vein embolization (PVE) before extended liver surgery is an accepted method to stimulate growth of the future liver remnant. Portal vein thrombosis (PVT) of the main stem and the non-targeted branches to the future liver remnant is a rare but major complication of PVE, requiring immediate revascularization. Without revascularization, curative liver surgery is not possible, resulting in a potentially life-threatening situation. We here present a new surgical technique to revascularize the portal vein after PVT by combining a surgical thrombectomy with catheter-based thrombolysis via the surgically reopened umbilical vein. This technique was successfully applied in a patient who developed thrombosis of the portal vein main stem, as well as the left portal vein and its branches to the left lateral segments after selective right-sided PVE in preparation for an extended right hemihepatectomy. The advantage of this technique is the avoidance of an exploration of hepatoduodenal ligament and a venotomy of the portal vein. The minimal surgical trauma facilitates additional intravascular thrombolytic therapy as well as the future right extended hemihepatectomy. We recommend this technique in patients with extensive PVT in which percutaneous less invasive therapies have been proven unsuccessful

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

Management of portal vein anastomotic stenosis after pediatric liver transplantation: Evaluation of single center experience

Introduction: Late onset portal vein anastomotic stenosis (PVAS) is a frequent complication in pediatric liver transplantation. For clinical relevant PVAS percutaneous transluminal angioplasty (PTA) is the first treatment option. When PTA is not feasible or not successful to obtain portal vein patency, a surgical Meso-portal shunt (MPS) can be performed. Our aim was to evaluate the clinical and biochemical characteristics of pediatric patients with post-transplant PVAS and the results of our management of these patients. Methods: We retrospectively studied all patients aged >18 years that underwent a therapeutic intervention procedure between 2014 and 2018, either PTA or MPS after pediatric liver transplantation including living and deceased liver donors. We evaluated primary patency of the PTA and MPS and secondary patency after the complete therapeutic intervention process. Results: PVAS was diagnosed by ultrasound and/or CT-scan prior to the first intervention. At our center, 18 (11%) of 165 patients underwent a therapeutic intervention procedure for PVAS after liver transplantation. Of the patients with PVAS, 72% had biliary atresia as the primary diagnosis, 72% were transplanted under 1 year of age and 67% received a living donor graft. All PVAS patients presented with splenomegaly. Thrombocyte counts were below 150 in only 67% of PVAS patients before the first intervention. Of all PVAS patients 44% had at least one episode of a gastro-intestinal bleeding. In 12 patients endoscopy was performed and all had esophageal varices. The median post-procedural follow-up time was 1.4 years. Twelve patients underwent a primary PTA, of whom one patient underwent two PTA's and one patient three PTA's in total. 10 patients received a MPS of whom four patients had a MPS after PTA. Primary patency was 67% for the first PTA, 0% for the second and third and patency after MPS was 80%. Secondary patency was 89% for the complete therapeutic approach. Conclusion: In 11% of our cohort of pediatric transplantation patients portal vein anastomotic stenosis is a significant problem especially in recipients with biliary atresia, transplantation below 1 year of age and after living donor transplantation. Based on our results we do not support a second PTA if the first PTA fails. Our combined treatment strategy with PTA and MPS has a good clinical outcome with a secondary patency of 89%

A systematic review and meta-analysis of endovascular and surgical revascularization techniques in acute limb ischemia

BACKGROUND: The initial treatment of patients with acute limb ischemia (ALI) remains undefined. The aim of this article was to compare the safety and effectiveness of catheter-driven thrombolysis (CDT) with surgical revascularization and evaluate the various fibrinolytic agents, endovascular, and pharmacochemical approaches that aim for thrombectomy. METHODS: PubMed, Embase, and the Cochrane Library were searched for studies on the management of ALI by means of surgical or endovascular recanalization, returning 520 studies. All randomized, controlled trials, nonrandomized prospective, and retrospective studies were included comparing treatment of ALI. RESULTS: Twenty-five studies, investigating a total of 4689 patients, were included for meta-analysis spread across nine different comparisons. No differences were found in limb salvage between thrombectomy and thrombolysis. More major vascular events were seen in the thrombolysis group (6.5% compared with 4.4% in the surgically treated group; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13-0.87; P = .02; I2 = 20%). Comparable limb salvage was found for high- and low-dose recombinant tissue plasminogen activator (r-tPA). No significant differences were found in major vascular event between low r-tPA (14%) and high r-tPA (10.5%; P = .13). The 30-day limb salvage rate was 79.7% for r-tPA treatment and 60.4% for streptokinase (OR, 3.14; 95% CI, 1.26-7.85; P = .01; I2 = 0%). AngioJet showed more limb salvage at 6 months compared with r-tPa (OR, 2.21; 95% CI, 1.17-4.18; P = .01; I2 = 0%). CONCLUSIONS: Both CDT and surgery have comparable limb salvage rates in patients with ALI; however, CDT is associated with a higher risk of hemorrhagic complications. No conclusions can be drawn regarding the risk of hemorrhagic complications regarding thrombolytic therapy by means of r-tPA, streptokinase, or urokinase. Insufficient data are available to conclude the preference of using a hybrid approach, ultrasound-accelerated CDT, heated r-tPA. or novel endovascular (rheolytical) thrombectomy systems. Future trials regarding ALI need to be constructed carefully, ensuring comparable study groups, and should follow standardized practices of outcome reporting

The use of perfusion CT for the evaluation of therapy combining AZD2171 with gefitinib in cancer patients

The purpose of this study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (CTP) in evaluating the hemodynamic response of tumors in the chest and abdomen treated with a combination of AZD2171 and gefitinib. Thirteen patients were examined just before and every 4-6 weeks after starting therapy. Following intravenous injection of a contrast agent, dynamic image acquisition was obtained at the level of a selected tumor location. To calculate perfusion, the maximum-slope method was used. Pre-treatment average perfusion for extra-hepatic masses was 84 ml/min/100 g, for liver masses arterial perfusion was 25 ml/min/100 g, and a portal perfusion of 30 ml/min/100 g was found. After the administration of AZD2171 and gefitinib, in extra-hepatic masses an initial decrease in perfusion of 18% was followed by a plateau and in liver masses an initial decrease of 39% within the lesions and of 36% within a rim region surrounding the lesions was followed by a tendency to recovery of hepatic artery flow. In conclusion, CTP is feasible in showing changes of perfusion induced by anti-angiogenic therapy

Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial

BACKGROUND: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. METHODS: Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. RESULTS: Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test). CONCLUSIONS: Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available

Endoscopic versus percutaneous biliary drainage in patients with resectable perihilar cholangiocarcinoma:a multicentre, randomised controlled trial

Background: In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma. Methods: We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 μmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243. Findings: From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15–11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64–1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage. Interpretation: The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease. Funding: Dutch Cancer Foundation

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study.

Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration &gt;10 BAU/mL and a previous SARS-CoV-2 infection as N IgG &gt;14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.</p

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort studyResearch in context

Summary: Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC