Nonmalignant portal vein thrombi in patients with cirrhosis consist of intimal fibrosis with or without a fibrin-rich thrombus.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT. APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi. CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy.

Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children.

BACKGROUND & AIMS: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. METHODS: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. RESULTS: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. LAY SUMMARY: Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.

Synchronous Unicentric Castleman Disease and Inflammatory Hepatocellular Adenoma: a Case Report.

Systemic symptoms such as fever and fatigue are non-specific manifestations spanning from inflammation to neoplasia. Here we report the case of a 34 year-old man who presented with systemic symptoms for four months. CT-scan and MRI revealed a 3.4 cm arterialized hepatic lesion and a 7 cm paraduodenal mass. Surgical resection of both lesions and histological examination revealed an inflammatory hepatocellular adenoma and a unicentric plasma cell type of Castleman disease. Moreover, a diffuse AA amyloid deposition in the liver was observed. Resection of both lesions was associated with an improvement of the symptoms. To our knowledge, this is the first report of a synchronous presentation of a unicentric plasma cell type of Castleman disease, inflammatory hepatocellular adenoma and AA amyloidosis.

Clinical and prognostic associations of liver volume determined by computed tomography in acute liver failure.

BACKGROUND: Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS: Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging. RESULTS: LV and PLV% showed marked variation when aetiologic groups were compared (P < .0001), including loss in cases with indeterminate cause (LV 939 cm3 [IQR 680-1259], PLV% 56% [42-84]) and increase in Budd-Chiari syndrome (1891 cm3 [1601-2094], 121% [111-131]). Progression to high-grade encephalopathy was more common with smaller LV and PLV. A < 1000 cm3 threshold identified NA patients who later developed it with 93% (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate disease with 91% (71-99) specificity and 63% (50-75) sensitivity. CONCLUSION: In patients with ALF/ALI, LV shows marked variation by the cause of disease, and in prognostic importance. In indeterminate and DILI cases, loss of volume to <1000 cm3 may indicate irreversible liver injury and regenerative failure and serve as an early clinical predictor for the development of high-grade encephalopathy and death.

Strategies to address the shortcomings of commonly used advanced chronic heart failure descriptors to improve recruitment in palliative care research: A parallel mixed-methods feasibility study.

BACKGROUND: Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients. AIM: To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients. DESIGN: A feasibility study using a pre-post uncontrolled design. SETTING: Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in Ireland Results: Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients. CONCLUSION: Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population.

Understanding how a palliative-specific patient-reported outcome intervention works to facilitate patient-centred care in advanced heart failure: A qualitative study.

BACKGROUND: Palliative care needs of patients with chronic heart failure are poorly recognised. Policy makers advise a patient-centred approach to holistically assess patients' needs and care goals. Patient-reported outcome measures are proposed to facilitate patient-centred care. AIM: To explore whether and how a palliative care-specific patient-reported outcome intervention involving the Integrated Palliative care Outcome Scale influences patients' experience of patient-centred care in nurse-led chronic heart failure disease management clinics. DESIGN: A feasibility study using a parallel mixed-methods embedded design was undertaken. The qualitative component which examined patients and nurses experience of the intervention is reported here. Semi-structured interviews were conducted and analysed using framework analysis. SETTING/PARTICIPANTS: Eligible patients attended nurse-led chronic heart failure disease management clinics in two tertiary referral centres in Ireland with New York Heart Association functional class II-IV. Nurses who led these clinics were eligible for inclusion. RESULTS: In all, 18 patients and all 4 nurses involved in the nurse-led clinics were interviewed. Three key themes were identified: identification of unmet needs, holistic assessment and patient empowerment. The intervention impacted on processes of care by enabling a shared understanding of patients' symptoms and concerns, facilitating patient-nurse communication by focusing on these unmet needs and empowering patients to become more involved in clinical discussions. CONCLUSION: This Integrated Palliative care Outcome Scale-based intervention empowered patients to become more engaged in the clinical consultation and to highlight their unmet needs. This study adds to the evidence for the mechanism of action of patient-reported outcome measures to improve patient-centred care and will help inform outcome selection for future patient-reported outcome measure research.

Primary Budd-Chiari Syndrome in Children: King's College Hospital Experience.

Primary Budd-Chiari syndrome is a rare cause of liver disease in children in the western world. Here we present a retrospective review of children with Primary Budd-Chiari syndrome presenting from January 2001 to November 2015 to our hospital. Seven children were identified. Their presentation was mostly chronic. All had predisposing factors for thrombosis and were started on anticoagulation. Radiological interventions (2 transjugular intrahepatic portosystemic shunts and 1 hepatic vein stenting), liver transplant and mesocaval shunt were done in 3, 2, and 1 patients, respectively; 1 child underwent bone marrow transplantation following transjugular intrahepatic portosystemic shunts and 1 child was managed only medically. After liver transplantation, one child died 3 years later as a result of subarachnoid haemorrhage, whereas others remain well at a median follow-up of 6 years. Despite high morbidity, the disease can have a good long-term outcome with a multidisciplinary approach.

Measures to assess commonly experienced symptoms for people with dementia in long-term care settings: a systematic review.

BACKGROUND: High symptom burden is common in long-term care residents with dementia and results in distress and behavioral challenges if undetected. Physicians may have limited time to regularly examine all residents, particularly those unable to self-report, and may rely on reports from caregivers who are frequently in a good position to detect symptoms quickly. We aimed to identify proxy-completed assessment measures of symptoms experienced by people with dementia, and critically appraise the psychometric properties and applicability for use in long-term care settings by caregivers. METHODS: We searched Medline, EMBASE, PsycINFO, CINAHL and ASSIA from inception to 23 June 2015, supplemented by citation and reference searches. The search strategy used a combination of terms: dementia OR long-term care AND assessment AND symptoms (e.g. pain). Studies were included if they evaluated psychometric properties of proxy-completed symptom assessment measures for people with dementia in any setting or those of mixed cognitive abilities residing in long-term care settings. Measures were included if they did not require clinical training, and used proxy-observed behaviors to support assessment in verbally compromised people with dementia. Data were extracted on study setting and sample, measurement properties and psychometric properties. Measures were independently evaluated by two investigators using quality criteria for measurement properties, and evaluated for clinical applicability in long-term settings. RESULTS: Of the 19,942 studies identified, 40 studies evaluating 32 measures assessing pain (n = 12), oral health (n = 2), multiple neuropsychiatric symptoms (n = 2), depression (n = 8), anxiety (n = 2), psychological wellbeing (n = 4), and discomfort (n = 2) were included. The majority of studies (31/40) were conducted in long-term care settings although none of the neuropsychiatric or anxiety measures were validated in this setting. The pain assessments, PAINAD and PACSLAC had the strongest psychometric evidence. The oral health, discomfort, and three psychological wellbeing measures were validated in this setting but require further psychometric evaluation. Depression measures were poor at detecting depression in this population. All measures require further investigation into agreement, responsiveness and interpretability. CONCLUSIONS: Measures for pain are best developed for this population and setting. All other measures require further validation. A multi-symptom measure to support comprehensive assessment and monitoring in this population is required.

How we treat sickle hepatopathy and liver transplantation in adults.

Sickle cell disease (SCD) has evolved into a debilitating disorder with emerging end-organ damage. One of the organs affected is the liver, causing "sickle hepatopathy," an umbrella term for a variety of acute and chronic pathologies. Prevalence of liver dysfunction in SCD is unknown, with estimates of 10%. Dominant etiologies include gallstones, hepatic sequestration, viral hepatitis, and sickle cell intrahepatic cholestasis (SCIC). In addition, causes of liver disease outside SCD must be identified and managed. SCIC is an uncommon, severe subtype, with outcome of its acute form having vastly improved with exchange blood transfusion (EBT). In its chronic form, there is limited evidence for EBT programs as a therapeutic option. Liver transplantation may have a role in a subset of patients with minimal SCD-related other organ damage. In the transplantation setting, EBT is important to maintain a low hemoglobin S fraction peri- and posttransplantation. Liver dysfunction in SCD is likely to escalate as life span increases and patients incur incremental transfusional iron overload. Future work must concentrate on not only investigating the underlying pathogenesis, but also identifying in whom and when to intervene with the 2 treatment modalities available: EBT and liver transplantation.

Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta-analysis.

OBJECTIVES: Multiple myeloma (MM) is an incurable haematological disease. Due to novel agents, overall survival has improved in this group, yet there are no systematic reviews to understand the symptom profiles resulting from disease and treatment-related toxicities. We aimed to synthesise data on the prevalence of symptoms in patients with MM. METHODS: A systematic database and grey literature search were conducted in six databases. Random-effects meta-analysis with inverse variance weighting to pool prevalence data was performed. RESULTS: Thirty-six studies were included of which 34 studies (N = 3023) provided data for meta-analysis. Twenty-seven distinct symptoms were reported, with the majority of studies focusing on pain (n = 27), fatigue (n = 19) and problems with functioning (n = 15). The most prevalent symptoms were fatigue (98.8%, 95% CI 98.1-99.2%), pain (73%, 39.9-91.7), constipation (65.2%, 22.9-92.2) and tingling in the hands/feet with 53.4% (0.4-99.7). The most common problems were decreased physical functioning (98.9%, 98.2-99.3), decreased cognitive functioning (80.2%, 40-96.1) and financial difficulties (78.4%, 39.1-95.4). These problems were present in newly diagnosed to advanced disease stage. CONCLUSIONS: Optimal quality of life and good symptom management in this incurable disease can only be achieved by routinely assessing symptoms throughout the disease trajectory.

Palliative care for advanced renal disease: a summary of the evidence and future direction.

BACKGROUND: Patients with end-stage kidney disease can have a significant symptom burden with complex co-morbidities. Compounding this is the choice between dialysis and conservative management. NEED FOR SUPPORTIVE AND PALLIATIVE CARE: For individuals with end-stage kidney disease, palliative care can provide support with symptom management, advance care planning and psychological support and education for both patients and their families. Optimum management may be achieved through collaboration between renal and palliative care professionals, combining their different skills in addressing symptom and medication management. Palliative and supportive care must be patient-centred to be effective. Multidisciplinary cross-organisational input is central to address the complex care needs of these patients, particularly for those in the community. WHAT IS KNOWN/WHAT IS NOT KNOWN: There is growing awareness of the need for research into the palliative care needs of those with end-stage kidney disease. Research has shown that patients receiving dialysis may prioritise quality of life over survival time, partly due to the constraints that they feel dialysis imposes on them. Systematic study of those opting for a conservative management pathway rather than dialysis is beginning to happen. RESEARCH IMPLICATIONS: Research is required into what underpins the preferences and priorities of patients with end-stage kidney disease to provide them with the best palliative and supportive care. POLICY AND PRACTICE: As more patients opt to follow the conservative pathway for their advanced renal disease, a change in service provision is required, with greater regular inclusion of palliative and supportive needs to address the gap in the care provision for this growing group.

Complications of congenital portosystemic shunts: liver tumors are affected by shunt severity, but pulmonary and neurocognitive associations are not.

BACKGROUND AND PURPOSE: Congenital portosystemic shunts (CPSS) are associated with multisystem complications, with the most common being liver tumors. The purpose of this study is to investigate the incidence of complications of CPSS, and to determine the natural history of liver tumors and their relationship with shunt closure. METHODS: Single-center retrospective cohort study of patients with CPSS referred from 1990 to 2020. Data on demographics, laboratory, radiological and histological investigations, clinical evolution, and surgery were reviewed. Mann-Whitney for continuous data and Fisher's exact test for categorical data were used. A p value of 0.05 was considered significant. RESULTS: 54 patients were investigated for CPSS with a median age of 1.1 years (IQR 0.2-11.8 years) at presentation-7 intrahepatic shunts resolved spontaneously and were excluded. Type 1 (without intrahepatic portal flow) had a higher rate of all hepatic tumors than Type 2 (partial intrahepatic portal flow) [18/22(82%) vs. 9/25(36%); p = 0.003); and malignant tumors (6/22(27%) vs 1/25(4%); (p = 0.04). Following shunt closure, 4/11(36%) of patients experienced partial and 3/11(27%) complete tumor regression. Pulmonary hypertension and hepatopulmonary syndrome affected 4(9%), and 3(6%) patients, respectively. Pulmonary complications affected 1 patient with Type 1 and 6 with Type 2 shunts (p = 0.1). Neurocognitive anomalies were identified in 16/47(34%) patients, 8/22(35%) with Type 1 shunts and 8/25(32%) with Type 2 shunts (p = 0.76). 9/47 (19%) required special needs schooling. CONCLUSIONS: Severity of portal venous deprivation (Type 1 CPSS) increases the risk of hepatic tumors and surgical closure is associated with a reduction in size or complete resolution of benign tumors.

Mixed phenotype hepatocellular carcinoma after transarterial chemoembolization and liver transplantation.

We investigated the phenotype of hepatocellular carcinoma (HCC) in livers removed during transplantation after local ablation therapy by transarterial chemoembolization (TACE). This study involved 80 HCC nodules (40 treated with TACE and 40 not treated with local ablation before transplantation) observed in 64 explanted livers and included clinicopathological evaluations as well as single and double immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), and CD133. HCCs with complete necrosis post-TACE without viable tumors were excluded from the analysis. Cholangiolar, glandular, or spindle cell areas suggestive of a mixed hepatocholangiocellular phenotype were seen in 14 post-TACE HCCs and in none of the non-TACE HCCs (P < 0.001). According to single-epitope immunohistochemistry of post-TACE HCCs, CD133, CK19, EpCAM, and NCAM were expressed in 14 (35%), 8 (20%), 12 (30%), and 8 (20%), respectively. Only EpCAM was detected in 4 non-TACE HCC cases (10%). RT-PCR experiments using tissues obtained by laser microdissection showed that 4 of 5 investigated post-TACE HCCs expressed at least 1 of the markers, which were coexpressed in 3 of 5 tumors, whereas CD133 and EpCAM were individually expressed in 2 non-TACE HCCs. Double immunostaining showed that CD133(+) cells frequently coexpressed CK19, EpCAM, or NCAM. Interestingly, the recurrence rate for patients with CD133(+) post-TACE HCC was significantly higher than the rate for patients with CD133(-) post-TACE HCC (P = 0.025). In conclusion, HCC with the combined hepatocholangiocellular phenotype appears to be more frequent in post-TACE HCC versus untreated HCC. Further studies are needed to investigate the potential relationships between TACE and HCC subpopulations with a chemoembolization-resistant phenotype and their clinical significance.

Selective embolization for bleeding visceral artery pseudoaneurysms in patients with pancreatitis.

BACKGROUND: Pancreatitis is associated with arterial complications in 4%-10% of patients, with untreated mortality approaching 90%. Timely intervention at a specialist center can reduce the mortality to 15%. We present a single institution experience of selective embolization as first line management of bleeding pseudoaneurysms in pancreatitis. METHODS: Sixteen patients with pancreatitis and visceral artery pseudoaneurysms were identified from searches of the records of interventional angiography from January 2000 to June 2007. True visceral artery aneurysms and pseudoaneurysms arising as a result of post-operative pancreatic or biliary leak were excluded from the study. RESULTS: In 50% of the patients, bleeding complicated the initial presentation of pancreatitis. Alcohol was the offending agent in 10 patients, gallstones in 3, trauma, drug-induced and idiopathic pancreatitis in one each. All 16 patients had a contrast CT scan and 15 underwent coeliac axis angiography. The pseudoaneurysms ranging from 0.9 to 9.0 cm affected the splenic artery in 7 patients: hepatic in 3, gastroduodenal and right gastric in 2 each, and left gastric and pancreaticoduodenal in 1 each. One patient developed spontaneous thrombosis of the pseudoaneurysm. Fourteen patients had effective coil embolization of the pseudoaneurysm. One patient needed surgical exclusion of the pseudoaneurysm following difficulty in accessing the coeliac axis radiologically. There were no episodes of re-bleeding and no in-hospital mortality. CONCLUSIONS: Pseudoaneurysms are unrelated to the severity of pancreatitis and major hemorrhage can occur irrespective of their size. Co-existent portal hypertension and sepsis increase the risk of surgery. Angiography and selective coil embolization is a safe and effective way to arrest the hemorrhage.

What are the main symptoms and concerns reported by patients with advanced chronic heart failure?-a secondary analysis of the Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS).

There is a lack of valid disease-specific patient-reported outcome measures (PROMs) for detecting symptoms and concerns in patients with advanced chronic heart failure (CHF). The Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS) are specifically developed to capture the main symptoms and concerns of people severely affected by advanced disease. The aim of this study was to determine whether POS and IPOS captures the main symptoms and concerns self-reported by patients with advanced CHF. A secondary analysis of existing POS/IPOS data collected in three longitudinal studies was conducted. POS and IPOS start with an open-ended question for patients to report their main problems and concerns, followed by subsequent closed questions on a range of symptoms and other concerns. Descriptive statistics were used to report the results. The 102 participants from the three datasets had median age 81 years (SD ±9.84 years); 62% male; 87% white. A total of 107 concerns were reported in the first, open POS/IPOS question seeking the patient's main concerns. Of these, 83 (77%) were reflected in the subsequent IPOS/POS closed questions. The high correspondence between the free-text responses and the closed questions indicates that most issues are captured by the POS/IPOS items. In conclusion, the generic versions of POS and IPOS do capture the main problems and concerns of patients with advanced CHF. Minor adaptations and further psychometric validation of POS and IPOS are needed in this population.

Complications from percutaneous microwave ablation of liver tumours: a pictorial review.

Percutaneous microwave ablation of liver tumours is a well-established technique that has been proven to be effective in the curative and palliative treatment of small volume primary and secondary liver tumours. Microwave ablation is designed to achieve larger areas of necrosis compared to radiofrequency ablation and has a good safety profile among liver tumour treatments. Mortality is unreported and major complications are rare. Knowledge of potential complications is essential for interventional radiologists performing liver ablation in order to reduce patient morbidity. The aim of this review is to illustrate major complications post microwave ablation in a pictorial format as well as a discussion on how best to avoid these complications.