Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial.

BACKGROUND: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. METHODS: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. RESULTS: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. CONCLUSIONS: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

Effect of Sarcopenia on the Increase in Liver Volume and Function After Portal Vein Embolization.

PURPOSE: Sarcopenia is associated with a decreased kinetic growth rate (KGR) of the future liver remnant (FLR) after portal vein embolization (PVE). However, little is known on the increase in FLR function (FLRF) after PVE. This study evaluated the effect of sarcopenia on the functional growth rate (FGR) after PVE measured with hepatobiliary scintigraphy (HBS). METHODS: All patients who underwent PVE at the Amsterdam UMC between January 2005 and August 2017 were analyzed. Functional imaging by HBS was used to determine FGR. Liver volumetry was performed using multiphase contrast computed tomography (CT). Muscle area measurement to determine sarcopenia was taken at the third lumbar level (L3). RESULTS: Out of the 95 included patients, 9 were excluded due to unavailable data. 70/86 (81%) patients were sarcopenic. In the multivariate logistic regression analysis, sarcopenia (p = 0.009) and FLR volume (FRLV) before PVE (p = 0.021) were the only factors correlated with KGR, while no correlation was found with FGR. 90-day mortality was similar across the sarcopenic and non-sarcopenic group (4/53 [8%] versus 1/11 [9%]; p = 1.000). The resection rates were also comparable (53/70 [75%] versus 11/16 [69%]; p = 0.542). CONCLUSION: FGR after PVE as measured by HBS appears to be preserved in sarcopenic patients. This is in contrast to KGR after PVE as measured by liver volumetry which is decreased in sarcopenic patients. LEVEL OF EVIDENCE: Level 3b, cohort and case control studies.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation.

BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

OBJECTIVE: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. BACKGROUND: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. METHODS: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. RESULTS: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. CONCLUSIONS: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Resectability of bilobar liver tumours after simultaneous portal and hepatic vein embolization versus portal vein embolization alone: meta-analysis.

BACKGROUND: Many patients with bi-lobar liver tumours are not eligible for liver resection due to an insufficient future liver remnant (FLR). To reduce the risk of posthepatectomy liver failure and the primary cause of death, regenerative procedures intent to increase the FLR before surgery. The aim of this systematic review is to provide an overview of the available literature and outcomes on the effectiveness of simultaneous portal and hepatic vein embolization (PVE/HVE) versus portal vein embolization (PVE) alone. METHODS: A systematic literature search was conducted in PubMed, Web of Science, and Embase up to September 2022. The primary outcome was resectability and the secondary outcome was the FLR volume increase. RESULTS: Eight studies comparing PVE/HVE with PVE and six retrospective PVE/HVE case series were included. Pooled resectability within the comparative studies was 75 per cent in the PVE group (n = 252) versus 87 per cent in the PVE/HVE group (n = 166, OR 1.92 (95% c.i., 1.13-3.25)) favouring PVE/HVE (P = 0.015). After PVE, FLR hypertrophy between 12 per cent and 48 per cent (after a median of 21-30 days) was observed, whereas growth between 36 per cent and 67 per cent was reported after PVE/HVE (after a median of 17-31 days). In the comparative studies, 90-day primary cause of death was similar between groups (2.5 per cent after PVE versus 2.2 per cent after PVE/HVE), but a higher 90-day primary cause of death was reported in single-arm PVE/HVE cohort studies (6.9 per cent, 12 of 175 patients). CONCLUSION: Based on moderate/weak evidence, PVE/HVE seems to increase resectability of bi-lobar liver tumours with a comparable safety profile. Additionally, PVE/HVE resulted in faster and more pronounced hypertrophy compared with PVE alone.

Current trends in regenerative liver surgery: Novel clinical strategies and experimental approaches.

Liver resections are performed to cure patients with hepatobiliary malignancies and metastases to the liver. However, only a small proportion of patients is resectable, largely because only up to 70% of liver tissue is expendable in a resection. If larger resections are performed, there is a risk of post-hepatectomy liver failure. Regenerative liver surgery addresses this limitation by increasing the future liver remnant to an appropriate size before resection. Since the 1980s, this surgery has evolved from portal vein embolization (PVE) to a multiplicity of methods. This review presents an overview of the available methods and their advantages and disadvantages. The first use of PVE was in patients with large hepatocellular carcinomas. The increase in liver volume induced by PVE equals that of portal vein ligation, but both result only in a moderate volume increase. While awaiting sufficient liver growth, 20%-40% of patients fail to achieve resection, mostly due to the progression of disease. The MD Anderson Cancer Centre group improved the PVE methodology by adding segment 4 embolization ("high-quality PVE") and demonstrated that oncological results were better than non-surgical approaches in this previously unresectable patient population. In 2012, a novel method of liver regeneration was proposed and called Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). ALPPS accelerated liver regeneration by a factor of 2-3 and increased the resection rate to 95%-100%. However, ALPPS fell short of expectations due to a high mortality rate and a limited utility only in highly selected patients. Accelerated liver regeneration, however, was there to stay. This is evident in the multiplicity of ALPPS modifications like radiofrequency or partial ALPPS. Overall, rapid liver regeneration allowed an expansion of resectability with increased perioperative risk. But, a standardized low-risk approach to rapid hypertrophy has been missing and the techniques used and in use depend on local expertise and preference. Recently, however, simultaneous portal and hepatic vein embolization (PVE/HVE) appears to offer both rapid hypertrophy and no increased clinical risk. While prospective randomized comparisons are underway, PVE/HVE has the potential to become the future gold standard.

Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation.

Background: Allograft biopsy is the gold standard for diagnosing graft rejection following simultaneous pancreas and kidney (SPK) transplant. Intraperitoneal biopsies are technically challenging and can be burdensome to patients and the healthcare system. Donor-derived cell-free DNA (dd-cfDNA) is well-studied in kidney transplant recipients; however, it has not yet been studied in the SPK population. Methods: We hypothesized that dd-cfDNA could be utilized for rejection surveillance following SPK transplant. We prospectively collected dd-cfDNA in 46 SPK patients at a single institution. Results: There were 10 rejection events, 5 of which were confirmed with biopsy. The other 5 were treated based on dd-cfDNA and clinical data alone with favorable outcomes. Among all patients who did not have rejection, 97% had dd-cfDNA <0.5%. Dd-cfDNA may also help differentiate rejection from graft injury (ie, pancreatitis) with median values in rejection 2.25%, injury 0.36%, and quiescence 0.18% (P = 0.0006). Conclusions: Similar to kidneys, dd-cfDNA shows promise for rejection surveillance in SPK transplant recipients.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients.

BACKGROUND: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. METHODS: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. RESULTS: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. CONCLUSION: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.

Is laparoscopic major hepatectomy feasible and safe in Swiss cantonal hospitals?

BACKGROUND: The number of laparoscopic liver resections is increasing worldwide, including in Switzerland. However, laparoscopy is mostly used for minor resections. Little is known about indications for and outcomes of major liver resections performed laparoscopically. The aim of this study was to compare the clinical outcome of open and laparoscopic major liver resection cohorts in two Swiss centres. METHODS: Patients undergoing open or laparoscopic major hepatectomy (>3 segments) in two cantonal hospitals from January 2015 to December 2019 were analysed. All disease types except perihilar cholangiocarcinomas, rare malignancies and resections with biliary reconstruction were included. The primary outcome was the number of complications incurred. Operation time, blood loss, hospital stay and 90-day mortality were secondary outcomes investigated. A separate analysis was performed for colorectal liver metastases, the most common indication. Potential risk factors for major complications were evaluated in a multivariate analysis. RESULTS: A total of 88 patients were identified. Among those, 34 patients underwent laparoscopic major hepatectomy (LAPH) and 54 patients open major hepatectomy (OH). The two groups did not differ in demographics. The most common indication was malignancy (LAPH 94% vs OH 98%), mainly colorectal liver metastases (LAPH 53% vs OH 59%). There was no significant difference in major complications (21% vs 15%, p = 0.565). Median operation time (LAPH 433 minutes, interquartile range [IQR 351-482 vs OH 397 minutes, IQR 296-446; p = 0.222), blood loss (325 ml, IQR 200-575 vs 475 ml, IQR 300-800; p = 0.150) and hospital stay (9 days, IQR 8-14 vs 11 days, IQR 9-14; p = 0.441) were comparable between the two cohorts. There was no significant difference in 90-day mortality (3% vs 7%, p = 0.881). The laparoscopic technique was not identified as a risk factor for major complications in a multivariate analysis. CONCLUSION: This first report from Switzerland evaluating outcomes of laparoscopic major hepatectomies showed no difference in complications and clinical non-inferiority compared with open major hepatectomy.

Intraoperative (Contrast-Enhanced) Ultrasound Has the Highest Diagnostic Accuracy of Any Imaging Modality in Resection of Colorectal Liver Metastases.

AIM: Defining sensitivity, specificity, diagnostic accuracy for detection of colorectal liver metastases in imaging compared to intraoperative assessment. Defining a cutoff, where accuracy of detection is impaired. METHODS: Prospective single-institution clinical trial (clinicaltrials.gov: NCT01522209). Patients underwent CEUS, MDCT, and 3 Tesla EOB-MRI within 2 weeks preoperatively. Intraoperative palpation, IOUS, and CEIOUS were performed. A patient and lesion-based database was analyzed for accuracy of detection of CEUS, CT, MRI, and Palp/IOUS/CEIOUS combined read. Histology was standard of reference. RESULTS: Forty-seven high tumor load (mean 5, 4 lesions) patients were analyzed. Histopathology confirmed 264 lesions (245 malignant: 19 benign). Accuracy for detection of all lesions: CEUS 63%, CT 71%, MRI 92%, and PALP/IOUS/CEIOUS 98%. ROC analysis for lesion size showed severe impairment of accuracy in lesion detection smaller than 5mm. Intraoperative imaging was not impaired by lesion size. Patient-based analysis revealed a change of resection plan after IOUS/CEIOUS in 35% of patients. CONCLUSION: At 5-mm lesion size, preoperative imaging shows a drop in accuracy of detection. In patients with multiple lesions, addition of MRI to MDCT seems useful. Accuracy of intraoperative ultrasound is not impacted by lesion size and should be mandatory. CEIOUS can improve intraoperative decision-making. TRIAL REGISTRATION: Study registered with clinicaltrials.gov : NCT01522209.

Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening.

To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable. SIGNIFICANCE: Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor.This article is highlighted in the In This Issue feature, p. 2355.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

Combined simultaneous embolization of the portal vein and hepatic vein (double vein embolization) - a technical note about embolization sequence.

BACKGROUND: Simultaneous portal vein embolization (PVE) and hepatic vein embolization (HVE) has been shown to be feasible, safe and lead to a faster growth of future liver remnant (FLR) than PVE alone. The objective of this study is to highlight different technical aspects as well as importance of embolization order. MATERIALS AND METHODS: Seven patients were treated with simultaneous PVE and HVE. In three cases, HVE was performed first followed by PVE and in four cases the other way around. Portal vein branches were embolized using Glubran-Lipiodol mixture in all cases. Hepatic veins were embolized using Amplatzer II plugs sized 8-20 mm. Specific consideration was given to depth of glue penetration in the portal vein defined by visible branch order on the treated side. RESULTS: Six of seven patients were discharged home the same day. One patient with infected tumor necrosis died of liver failure 40 days later, otherwise there were no periprocedural clinical complications. Median glue penetration was to the 5th order (4th - 5th) when PVE was performed first and 3rd order (2nd - 4th) when PVE was performed after HVE. In one PVE first case, glue spillage was seen due to marked reduced flow in the right portal vein. There was sufficient FLR growth for subsequent surgical resection in the remaining six patients. CONCLUSION: PVE should be performed prior to HVE because the reduced flow in the portal vein after HVE leads to less deep glue penetration with presumably increased risk of contralateral spillage.