EUS-Guided Thrombin Injection and Coil Implantation for Gastric Varices: Feasibility, Safety, and Outcomes.

BACKGROUND AND AIMS: Gastric varices (GV) are reported in up to 20% of patients with portal hypertension, and bleeding is often more severe and challenging than oesophageal variceal bleeding. There is limited data on prophylaxis of GV bleeding or management in the acute setting, and different techniques are utilised. This study aims to evaluate outcomes following endoscopic ultrasound (EUS) guided placement of coils in combination with thrombin to manage GV. METHODS: We retrospectively reviewed all patients treated with combination EUS-guided therapy with coils and thrombin between October 2015 and February 2020. RESULTS: 20 patients underwent 33 procedures for GV therapy; 16/20 (80%) were type 1 Isolated GV (IGV1), and the remainder were type 2 Gastroesophageal Varices (GOV2). Median follow-up was 842 days (Interquartile range (IQR) 483-961). 17/20 (85%) had underlying cirrhosis, the most common aetiologies being alcohol-related liver disease and non-alcoholic steatohepatitis (NASH). The median Child-Pugh (CP) score was 6 (IQR 5-7). In 11/20 (55%) cases, the indication was secondary prophylaxis to prevent rebleeding; in 2/20 (10%), the bleeding was acute. Technical success was achieved in 19/20 (95%) of cases. During follow-up, the obliteration of flow within the varices was achieved in 17/20 (85%) cases. The 6-week survival was 100%, and 2 adverse events were reported: cases of rebleeding at day 5 and day 37; both rebleeds were successfully managed endoscopically. CONCLUSIONS: EUS-guided GV obliteration combining coil placement with thrombin, in our experience, is technically safe with good medium-term efficacy. A multicenter randomised controlled trial comparing different treatment strategies would be desirable to understand options better.

Technical and clinical outcomes following EUS-guided thrombin injection and coil implantation for parastomal varices.

BACKGROUND AND AIMS: Bleeding from parastomal varices causes significant morbidity and mortality. Treatment options are limited, particularly in high-risk patients with significant underlying liver disease and other comorbidities. The use of EUS-guided embolisation coils combined with thrombin injection in gastric varices has been shown to be safe and effective. Our institution has applied the same technique to the treatment of parastomal varices. METHODS: A retrospective review was performed of 37 procedures on 24 patients to assess efficacy and safety of EUS-guided injection of thrombin, with or without embolisation coils for treatment of bleeding parastomal varices. All patients had been discussed in a multidisciplinary team meeting, and correction of portal hypertension was deemed to be contraindicated. Rebleeding was defined as stomal bleeding that required hospital admission or transfusion. RESULTS: All patients had significant parastomal bleeding at the time of referral. 100% technical success rate was achieved. 70.8% of patients had no further significant bleeding in the follow-up period (median 26.2 months) following one procedure. 1-year rebleed-free survival was 80.8% following first procedure. 7 patients (29.1%) had repeat procedures. There was no significant difference in rebleed-free survival following repeat procedures. Higher age was associated with higher risk of rebleeding. No major procedure-related complications were identified. CONCLUSIONS: EUS-guided thrombin injection, with or without embolisation coils, is a safe and effective technique for the treatment of bleeding parastomal varices, particularly for patients for whom correction of portal venous hypertension is contraindicated.

Textbook Outcome After Trans-arterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: Textbook Outcome (TO) is inclusive of quality indicators and it not been provided for trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data on treatment-naïve HCC patients receiving TACE from 10 centers were reviewed. TO was defined as "no post-TACE grade 3-4 complications, no prolonged hospital stay (defined as a post-procedure stay ≤ 75th percentile of the median values from the total cohort), no 30-day mortality/readmission and the achievement of an objective response (OR) at post-TACE imaging." Grade of adverse event was classified according to the Common Terminology Criteria for Adverse Events and short-term efficacy was assessed by response. Pooled estimates were calculated to account for hospital's effect and risk-adjustment was applied to allow for diversity of patients in each center. RESULTS: A total of 1124 patients (2014-2018) fulfilling specific inclusion criteria were included. Baseline clinical features showed considerable heterogeneity (I2 > 0.75) across centers. TACE-related mortality was absent in 97.6%, readmission was not required after 94.9% of procedures, 91.5% of patients had no complication graded 3-4, 71.8% of patients did not require prolonged hospitalization, OR of the target lesion was achieved in 68.5%. Risk-adjustment showed that all indicators were achieved in 43.1% of patients, and this figure was similar across centers. The median overall survival for patients who achieved all indicators was 33.1 months, 11.9 months longer than for patients who did not. CONCLUSIONS: A useful benchmark for TACE in HCC patients has been developed, which provides an indication of survival and allows for a comparison of treatment quality across different hospitals.

'Potentially curative therapies' for hepatocellular carcinoma: how many patients can actually be cured?

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that 'curative therapies' can be successfully applied. The term 'curative' is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various 'curative' therapies. METHODS: We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies. RESULTS: The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours. CONCLUSION: Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a 'calculator' that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.

Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria.

BACKGROUND: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. METHOD: Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. RESULTS: Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77-2.67). The median follow-up period was 5.1 95% CI [4.7-5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51-10.59], P < 0.001) and body mass index (0.74 95% CI [0.59-0.89], P < 0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 - 1.94], P = 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96-0.99], P = 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P = 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 - 2.05], P = 0.036) and SMI were (HR 0.98 95% CI [0.95-0.99], P = 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. CONCLUSIONS: Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.

Biopsy for advanced hepatocellular carcinoma: results of a multicentre UK audit.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK. METHODS: This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0-2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form. RESULTS: Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding. CONCLUSION: The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy.

Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death.

OBJECTIVE: The aim of this study was to investigate tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC), with and without hypothermic oxygenated liver perfusion (HOPE) before transplantation. PATIENTS AND METHODS: We analyzed all liver recipients with HCC, transplanted between January 2012 and September 2019 with donation after circulatory death (DCD) livers after previous end-ischemic HOPE-treatment (n = 70, Center A). Tumor parameters and key confounders were compared to consecutive recipients with HCC, transplanted during the same observation period with an unperfused DBD liver (n = 70). In a next step, we analyzed unperfused DCD (n = 70) and DBD liver recipients (n = 70), transplanted for HCC at an external center (Center B). RESULTS: Tumor parameters were not significantly different between HOPE-treated DCD and unperfused DBD liver recipients at Center A. One-third of patients were outside established tumor thresholds, for example, Milan criteria, in both groups. Despite no difference in tumor load, we found a 4-fold higher tumor recurrence rate in unperfused DBD livers (25.7%, 18/70), compared to only 5.7% (n = 4/70) recipients with tumor recurrence in the HOPE-treated DCD cohort (P = 0.002) in Center A. The tumor recurrence rate was also twice higher in unperfused DCD and DBD recipients at the external Center B, despite significant less cases outside Milan. HOPE-treatment of DCD livers resulted therefore in a 5-year tumor-free survival of 92% in HCC recipients, compared to 73%, 82.7%, and 81.2% in patients receiving unperfused DBD or DCD livers, from both centers. CONCLUSION: We suggest that a simple machine liver perfusion approach appears advantageous to protect from HCC recurrence after liver transplantation, despite extended tumor criteria.

The Impact of Direct-acting Antivirals on Overall Mortality and Tumoral Recurrence in Patients With Hepatocellular Carcinoma Listed for Liver Transplantation: An International Multicenter Study.

BACKGROUND: There is a lack of data on the use of direct-acting antivirals (DAA) on the risk of death and tumoral recurrence in patients with hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) listed for liver transplantation (LT). We aimed to assess the impact of antiviral treatment on mortality and HCC recurrence patients with HCC-HCV. METHODS: This was a retrospective multicenter study of patients with HCC-HCV listed for LT from 2005 to 2015. Patients were divided according to the antiviral treatment received after HCC diagnosis: DAA, interferon (IFN), or no antiviral. Intention-to-treat overall survival and HCC recurrence incidence were compared by the Kaplan-Meier method. Multivariable regression analysis was performed to identify risk factors for outcomes. RESULTS: A total of 1012 HCV-HCC patients were listed for LT during the study period. The median follow-up was 4.0 (interquartile range = 2.3-6.7) years. Mortality was 5.6 (95% confidence interval [CI], 4.3-7.2), 13.1 (95% CI, 11.0-15.7), and 6.2 (95% CI, 5.4-7.2) deaths per 100 person-year among patients treated with DAA, IFN, and antiviral naïve, respectively (P < 0.001). Of the 875 HCV-HCC transplant recipients, the 5-year recurrence-free survival was 93.4%, 84.8%, 73.9% for the pre-LT DAA, pre-LT IFN, and antiviral naïve groups, respectively (P < 0.001). After multivariable regression, the use of pre-LT DAA was not associated to risk of recurrence (hazard ratio = 0.44 [95% CI, 0.19-1.00]). Post-LT DAA was not related to increased risk of recurrence (hazard ratio = 0.62 [95% CI, 0.33-1.16]). CONCLUSIONS: In this multicenter intent-to-treat study, DAA therapy was not found to be a risk factor for mortality or HCC recurrence after adjusting for potential confounders.

Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma.

Scavenger receptor class F member 1 (SCARF1) is thought to play an important role in the selective recruitment of CD4+ T cells to liver sinusoidal endothelial cells during chronic liver disease. However, the contribution of SCARF1 to hepatocellular carcinoma (HCC) is currently unknown. We utilized publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to explore SCARF1 expression in HCC and correlated it with a number of clinicopathological features. Flow adhesion assays were used to determine the role of SCARF1 in CD4+ T cell subset recruitment. SCARF1 expression was downregulated in HCC tumor tissues, compared to non-tumoral tissues, and loss of SCARF1 expression was associated with poorly differentiated/aggressive tumors. Additionally, higher SCARF1 expression in HCC tumor tissues was highly prognostic of better overall, disease-free and progression-free survival. SCARF1 within HCC was largely associated with tumor endothelial cells and adhesion studies suggested that it played a role in the specific recruitment of proinflammatory CD4+ T cells (CD4+CD25-) to HCC tumor tissues. Endothelial SCARF1 expression in tumor biopsies may provide critical prognostic information. Additionally, SCARF1 may also be a novel endothelial target that could help re-programme the microenvironment of HCC by promoting effector T cell tumor infiltration.

Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer.

Hepatocellular carcinoma (HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.

Radiological insertion of automated low flow ascitic pump (alfapump®) system for management of medically refractory ascites.

Ascites is well-documented sequelae of liver cirrhosis with significant impact on survival in this group of patients. Among the many established management strategies for the same is the use of an implantable mechanical device, called alfapump® (Sequana Medical, Zurich, Switzerland), that removes ascitic fluid by pumping it from the peritoneal cavity to the urinary bladder. Until recently, this device has been surgically placed under general anaesthesia. We describe successful interventional radiological implantation under conscious sedation in three patients with minimal complications. This device can serve as an alternative to transjugular intrahepatic portosystemic shunt for the management of refractory ascites; however, further studies are required to understand the device better.

An unusual presentation of an amoebic liver abscess: the story of an unwanted souvenir.

This case was rather unusual with regard to the disease presentation. The patient had non-specific symptoms of weight loss and general malaise, without any history of preceding diarrhoea or dysentery. It is important to be aware of the epidemiology of the disease, and to relate it to patients presenting with symptoms suggestive of amoebiasis. We discuss the recommended investigations and management options for these patients based on the current guidelines/evidence.

Providing Spatial Data for Secondary Analysis: Issues and Current Practices relating to Confidentiality.

Spatially explicit data pose a series of opportunities and challenges for all the actors involved in providing data for long-term preservation and secondary analysis -- the data producer, the data archive, and the data user. We report on opportunities and challenges for each of the three players, and then turn to a summary of current thinking about how best to prepare, archive, disseminate, and make use of social science data that have spatially explicit identification. The core issue that runs through the paper is the risk of the disclosure of the identity of respondents. If we know where they live, where they work, or where they own property, it is possible to find out who they are. Those involved in collecting, archiving, and using data need to be aware of the risks of disclosure and become familiar with best practices to avoid disclosures that will be harmful to respondents.

Solving problems of disclosure risk while retaining key analytic uses of publicly released microdata.

MEASURES USED TO PROTECT SUBJECTS in publicly distributed microdata files often have a significant negative impact on key analytic uses of the data. For example, it may be important to analyze subpopulations within a data file such as racial minorities, yet these subjects may present the greatest disclosure risk because their records tend to stand out or be unique. Files or records that are linkable create another type of disclosure risk-common elements between two files can be used to link files with sensitive data to externally available files that disclose identity. Examples of disclosure limitation methods used to address these types of issues include blanking out data, coarsening response categories, or withholding data altogether. However, the very detail that creates the greatest risk also provides insight into differences that are of greatest interest to analysts. Restricted-use agreements that provide unaltered versions of the data may not be available, or only selectively so. The public-use version of the data is very important because it is likely to be the only one to which most researchers, policy analysts, teaching faculty, and students will ever have access. Hence, it is the version from which much of the utility of the data is extracted and often it effectively becomes the historical record of the data collection. This underscores the importance that the disclosure review c ommittee s trikes a g ood b alance b etween protection and u tility. In this paper we d escrib e our disclosure review committee's (DRC) analysis and resulting data protection plans for two national studies and one administrative data system. Three distinct disclosure limitation methods were employed, taking key uses of the data into consideration, to protect respondents while still providing statistically accurate and highly useful public-use data. The techniques include data swapping, microaggregation, and suppression of detailed geographic data. We describe the characteristics of the data sets that led to the selection of these methods, provide measures of the statistical impact, and give details of their implementations so that others may also utilize them. We briefly discuss the composition of our DRC, highlighting what we believe to be the important disciplines and experience represented by the group.