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Transarterial chemoembolization (TACE) is the treatment of choice for intermediate-stage hepatocellular carcinoma (HCC). Recent data suggest that TACE may boost the efficacy of anti-PD-1 immunotherapy. The authors present the trial protocol for PETAL, a phase Ib study, which will assess the safety and bioactivity of pembrolizumab, an anti-PD-1 antibody, following TACE in HCC. After a run-in phase evaluating six patients to establish preliminary safety, up to 26 additional participants will be enrolled. Pembrolizumab will be administered three-times weekly for 1 year or until progression, starting 30–45 days after TACE. The primary objective is to determine safety and the secondary objective is to preliminarily evaluate efficacy. Radiological responses will be evaluated every four cycles. Clinical Trial Registration: NCT03397654 ( ClinicalTrials.gov )

Venturi tubes are widely used to measure the gas flow rate in a wet-gas stream. To calculate the gas flow rate, wet-gas Venturi tubes require the liquid loading (i.e. Lockhart-Martinelli parameter) to be known as an input to a so-called over-reading correction correlation. It is challenging to derive the Lockhart-Martinelli parameter without installing additional devices in series to the Venturi tube thus adding significant cost and complexity. A relatively low cost and easy to implement method is to derive the Lockhart-Martinelli parameter by measuring the pressure drop across the Venturi tube or along a pipe section. A correlation that predicts the Lockhart-Martinelli parameter by measuring the pressure drop along a vertical pipe section downstream of the Venturi tube is presented. The correlation was obtained by fitting experimental results from TUV-SUD National Engineering Laboratory's wet-gas test facility with nitrogen-water in a 4″ vertical pipe, Lockhart-Martinelli from 0.04 to 0.29, and gas Froude number from 1 to 2.7. Further experiments were conducted at Spirax Sarco Engineering plc to evaluate the performance of the proposed correlation under steam-water conditions. Tests were conducted with steam-water in a vertical 2″ pipe, Lockhart-Martinelli from 0.005 to 0.064, and gas Froude number from 0.55 to 1.35. The Lockhart-Martinelli parameter is predicted within ±0.035 absolute value with the proposed new correlation for both the National Engineering Laboratory and Spirax Sarco datasets. Gas flow rate values within approximately ±5% error are obtained with the proposed correlation together with ISO/TR 11583 over-reading correlation for the NEL dataset. Although further improvements to the proposed method are required, this work demonstrates the efficacy of an agile, simple, and low-cost differential pressure method to aid the Venturi meter to determine the gas mass flow rate in wet-gas flow.

Objectives Sinistral portal hypertension (SPH) is caused by increased pressure on the left portal system secondary to splenic vein stenosis or occlusion and may lead to gastric varices. The definitive management of SPH is splenectomy, but this is associated with significant mortality and morbidity in the acute setting. In this systematic review, we investigated the efficacy and safety of splenic artery embolisation (SAE) in managing refractory variceal bleeding in patients with SPH. Methods A comprehensive literature search was conducted using MEDLINE and Embase databases. A qualitative analysis was chosen due to heterogeneity of the studies. Results Our search yielded 339 articles, 278 of which were unique. After initial screening, 16 articles relevant to our search remained for full text review. Of these, 7 were included in the systematic review. All 7 papers were observational, 6 were retrospective. Between them they described 29 SAE procedures to control variceal bleeding. The technical success rate was 100% and there were no cases of rebleeding during follow up. The most common complication was post-embolisation syndrome. Four major complications occurred, two resulting in death. These deaths were the only 30-day mortalities recorded and were in patients with extensive comorbidities. Conclusions Although there is a distinct lack of randomized controlled studies comparing SAE to other treatment modalities, it appears to be safe and effective in treating hemorrhage secondary to SPH.

The measurement of void fraction in multiphase flow is important for a wide range of industrial processes. Existing methods for void fraction measurement require intrusive, expensive and potentially hazardous equipments which constrict the flow, adding both capital and operational costs. Two phase flow experiments were carried out at the National Engineering Laboratory (NEL) to measure void fraction via pressure drop in a vertical pipe. Additional experiments are carried out at Spirax Sarco Inc. to validate the efficacy of the method on steam/water flow mixtures at high temperature and pressure, in gas mass fraction range between 0.17 and 0.95 and void fraction range between 0.75 and 1.0. The void fraction calculated by the presented differential pressure (dP) method is confirmed via established correlations. The work demonstrates the efficacy of a low cost, non-intrusive method to determine void fraction in two phase flow over a wide range of flow conditions.

Objectives: Common terminal phase symptoms include pain, dyspnoea, anxiety, terminal restlessness, nausea and noisy breathing. This study identified the proportion of community pharmacies across tw...

4093 Background: Early-stage hepatocellular carcinoma (HCC) can be treated with liver resection (LR), but up to 70% of patients experience relapse within two years after surgery. Despite their established use in advanced disease, immune checkpoint inhibitors (ICPI) are still under investigation in the peri-operatory setting. Methods: PRIME‐HCC is a phase Ib study investigating safety and bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus ipilimumab (1mg/kg, day 1 only) combination (Nivo+Ipi) prior to LR in early-stage HCC. The primary safety analysis assessed treatment-related adverse events (trAE) and delays to surgery. Secondary endpoint included objective response rate (ORR) by RECIST v1.1 and pathologic response rate on resection specimens. Results: At data censoring on the 27th of January 2022, 17 patients were enrolled, of whom 82% (n = 14) were male, with a median age of 64 years (range 47-76). Performance status was 0 in 88% of patients (n = 15) according to the Eastern Cooperative Oncology Group scale. Liver cirrhosis was found in 65% (n = 11) of the patients, mostly secondary to viral hepatitis (41%, n = 7). All patients were Child-Pugh A, with 53% (n = 9) classified as albumin-bilirubin (ALBI) grade 2, and the rest grade 1. Median tumour diameter was 3.4 cm (interquartile range [IQR] 2.4-4.0), and the median number of liver nodules was 1 (range 1-3). Any-grade trAEs were reported by 73% of the patients receiving at least one dose of treatment (n = 11, tot n = 15). Four patients (27%) reported grade 2 trAEs including hypothyroidism (n = 2), diarrhoea (n = 1), and fatigue (n = 1), and one (7%) grade 3 ALT/AST elevation. After a median follow-up of 6.3 months (IQR 1.9-23.0), no deaths had occurred. One patient had experienced relapse 20.8 months after treatment commencement, and he achieved partial response to subsequent treatment with atezolizumab plus bevacizumab. Median time to LR from screening was 2.5 months (IQR 2.3-3.2). Only one patient had a surgery delay due to liver function worsening (ICPI-unrelated) and experienced disease progression 12.4 months post-screening. One patient was found to have cholangiocarcinoma (CCA) on LR specimen and was excluded from efficacy analyses. Of the 13 patients with an available radiological assessment, ORR was 23%, with two partial responses and one complete response. Disease control rate was 92%, with one patient with mixed HCC/CCA histology showing primary progression. Of the nine pathologically evaluable patients, seven (78%) achieved a pathological response, including two (22%) complete responses. Conclusions: Nivo+Ipi can be safely administered in the neoadjuvant setting for HCC and does not delay LR. The combination demonstrates promising evidence of anti-tumour efficacy in terms of radiological and pathological response. Clinical trial information: NCT03682276.

e16195 Background: Trans-arterial chemoembolization (TACE) is the gold-standard for intermediate stage HCC. We hypothesised the ischemic and cytotoxic effect of TACE to boost anti-cancer immunity and to synergise with the anti PD-1 pembrolizumab (pembro). We designed a phase Ib study to test the safety and preliminary efficacy of pembro after TACE in intermediate HCC. Methods: PETAL study will enroll up to 32 patients with intermediate HCC to receive pembro 200 mg every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. The first safety-run-in phase includes 6 patients: if no dose limiting toxicities (DLTs) emerge over a 21-day window after first pembro, the others are enrolled in the expansion phase. Pembro is given within 30 days after 1 or 2 TACEs. The first phase includes 1 patient scoring Child-Pugh (CP)-B7 and the remaining have to be CP-A. Safety is the primary endpoint and is measured as the incidence of treatment-related adverse events (TRAEs), graded according to NCI CTCAEv4. Efficacy is the secondary endpoint and is evaluated as progression free survival (PFS) from first TACE, according to mRECIST criteria. Survival is estimated using Kaplan-Meier method. All the patients who have received at least one dose of pembro are evaluable for safety. Results: At the time of data cut-off, on the 14th of January 2022, 14 patients had received at least one dose of pembro. The median age was 72 (IQR: 63.3-74.6), 79% were male, 71% were cirrhotic, 29% had viral hepatis and 43% ECOG PS 1. One patient had Child-Pugh (CP) class B7 and 13 had A. The median number of nodules was 1.5 (IQR:1-2.8), and 4.1 cm (IQR: 3.7-4.5) the median diameter. Overall, 5 patients received 2 TACEs and 9 had 1. Patients received a median of 4.5 cycles (IQR: 2.3-6.5) of pembro. No DLTs emerged in the first phase. Treatment-related adverse events (TRAE) of any grade (G) were reported in 86% of participants, 21% of participants experienced G3 TRAEs, and there were no G4 or G5 TRAEs. Specific skin-related toxicity was the most frequently reported (35%) TRAE. No patients had treatment-related liver toxicity. Causes of treatment discontinuation were PD (n=7), TRAEs (n=1), clinical deterioration in the CP B patient (n=1), COVID pandemic (n=2) and withdrawal of consent (n=1); at the time of data cut-off, mPFS from first TACE was 10.8 months (95%CI: 6.63-14.97). Conclusions: Adjuvant pembro following TACE is manageable and tolerable with signs of activity. These results prompt the investigation in larger trials. Clinical trial information: NCT03397654. [Table: see text]

As the population ages, the number of older populations globally requiring palliative care is rapidly growing, requiring services of multidisciplinary teams—including community pharmacists. The aim of this study is to describe the community pharmacists’ perceived role in providing services to community dwelling older Australians receiving palliative care. Utilising an eight-domain End of Life Directions for Aged Care (ELDAC) care model, a national cross-sectional questionnaire was designed and undertaken online with Australian community pharmacists. Respondents were asked questions relating to socio-demographic characteristics, practice characteristics, and scope of services provided. Of the 62 pharmacists who responded to the questionnaire, 51 were included in the final data analysis and reporting. Pharmacists working in dispensing roles made up about half of the respondents, while the remainder worked in settings such as general practice, residential aged care, or providing medication review services. Pharmacists can identify patients with indicators of poor life expectancy and mostly work with older Australians daily. Dispensing and non-dispensing pharmacists offer a range of services that complement each other. Organisations caring for the aged should consider the role of the pharmacist, in caring for people with palliative care needs, along with their carers.

Background After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. Methods The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. Discussion The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. Trial registration EudraCT Number: 2018–000987-27 Clinical trial registry & ID: ClinicalTrials.gov: NCT03682276.

Background: For most people, the last 12 months of life are spent living in the community, with the support of family and friends for a number of caregiving functions. Previous research has found that managing medicines is challenging for caregivers. Currently there is little information describing which caregivers may struggle with tasks associated with managing a loved one's medicines. Aim: The aim of this study was to identify factors that flag caregivers who are likely to experience problems when managing someone else's medications. Setting/Participants: The annual South Australian Health Omnibus Survey provides a face-to-face, cross-sectional, whole-of-population view of health care. Structured interviews, including questions covering palliative care and end-of-life care, were conducted with 14,625 residents in their own homes. Results: Of the 1068 respondents who had provided care for someone who died of a terminal illness in the last five years, 7.4% identified that additional support with medicine management would have been beneficial. In addition, three factors were predictive of the need for additional support in managing medicines: aged

Background Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. Methods A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. Results Median OS was 15.4 months. Tumour size > 7 cm (p 7 cm, ITN and AEN identified patients with poor prognosis (p

Background Evidence exists for the use of palliative sedation for people approaching the last days of life with refractory and intolerable symptoms. It is a third-line intervention that deliberately lowers the conscious state to relieve intolerable and refractory symptoms. This level of intervention is not routinely used in primary care, and there is a lack of guidelines for palliative sedation in this context. Objective This article provides some key information about palliative sedation and global issues faced by all individuals involved. A tertiary centre case study is used to illustrate the key points. Given this form of therapy may be required for palliative patients in the community, another aim of this article is to provide an overview for primary care practitioners to raise their awareness of such therapy and the issues related to it. Discussion While palliative sedation has been regarded as 'controversial' in early palliative care literature, there has been an increased effort to formulate standardised guidelines to define and ethically justify this procedure.

// David J. Pinato 1 , Tadaaki Arizumi 2 , Jeong Won Jang 3 , Elias Allara 4, 5 , Puvan I. Suppiah 1 , Carlo Smirne 4 , Paul Tait 6 , Madhava Pai 7 , Glenda Grossi 4 , Young Woon Kim 3 , Mario Pirisi 4, 8 , Masatoshi Kudo 2 , Rohini Sharma 1 1 Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK 2 Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan 3 Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Seoul, Republic of Korea 4 Department of Translational Medicine, Universita degli Studi del Piemonte Orientale “A. Avogadro”, Novara, Italy 5 School of Public Health, Universita degli Studi di Torino, Torino, Italy 6 Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, London, UK 7 Department of Surgery, Imperial College NHS Trust, Hammersmith Hospital, London, UK 8 Interdisciplinary Research Center of Autoimmune Diseases, Universita degli Studi del Piemonte Orientale “A. Avogadro”, Novara, Italy Correspondence to: David James Pinato, email: david.pinato@imperial.ac.uk Keywords: prognosis, hepatocellular carcinoma, TACE, ART score, HAP score Received: February 22, 2016 Accepted: April 26, 2016 Published: May 26, 2016 ABSTRACT Background: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. Results: In both training and validation sets, HAP and ART scores emerged as independent predictors of OS ( p

Process analyzers for in-situ monitoring give advantages over the traditional analytical methods such as their fast response, multi-chemical information from a single measurement unit, minimal errors in sample handing and ability to use for process control. This study discusses the suitability of Raman spectroscopy as a process analytical tool for in-situ monitoring of CO2 capture using aqueous monoethanolamine (MEA) solution by presenting its performance during a 3-day test campaign at PACT pilot plant in Sheffield, UK. Two Raman immersion probes were installed on lean and rich streams for real time measurements. A multivariate regression model was used to determine the CO2 loading.The plant performance is described in detail by comparing the CO2 loading in each solvent stream at different process conditions. The study shows that the predicted CO2 loading recorded an acceptable agreement with the offlinemeasurements. The findings from this study suggest that Raman Spectroscopy has the capability to follow changes in process variables and can be employed for real time monitoring and control of the CO2 capture process. In addition,these predictions can be used to optimize process parameters; to generate data to use as inputs for thermodynamic models, plant design and scale-up scenarios.

Quality of life (QoL) in patients with colorectal cancer and liver metastases treated with selective internal radiotherapy (SIRT) using Yttrium-90 resin microspheres combined with FOLFOX (standard chemotherapy) has not been compared to FOLFOX alone. We report QoL results from a prospectively pooled analysis of 3 multicentre randomized trials: FOXFIRE, FOXFIRE-Global and SIRFLOX.

The role of the hospice is well established in providing quality care for the dying. With the drive for greater emphasis on community-based palliative care, there is a need to enable elements (especially medicines management practices) from the inpatient hospice model to be more readily available in the community environment. This paper describes the incorporation of an advanced practice pharmacist into a large metropolitan palliative care service. The focus of this appointment has been to develop strategic engagement with primary care providers to better support medicines management for people registered within a metropolitan palliative care service. Through the development of education programs, participation in quality improvement activities and by supporting the ambulatory palliative care team, the advanced practice pharmacist has engaged the community pharmacist as part of the broader palliative care team. There are challenges and opportunities for pharmacists to assist in providing improved palliative care services delivery within the Australian healthcare system.

Background The efficacy of TACE is secondary to its dual ischaemic and cytotoxic effect, which promotes immunogenic tumor cell death. TACE may prime adaptive immunity and facilitate pembrolizumab (pembro; anti-PD1) in promoting tumour immune rejection and improve outcome in HCC. We designed this phase Ib study to evaluate safety, preliminary activity of TACE+pembrolizumab and explore mechanisms of efficacy. Methods Up to 32 patients (pts) with intermediate-stage HCC were planned to receive up to 2 rounds of conventional TACE followed by pembro 200mg q3w 30 days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety with dose-limiting toxicities emerging from the combination being evaluated over a 21-days window from commencement of pembro. Secondary endpoints included PFS rates q12w. We explored tumour and host determinants of response in tissue, blood and stool samples to confirm the bioactivity of the combination. Results In cohort 1 (n=6) patients were all of BCLC-B stage, 83% males, 16% HCV-positive, 50% ECOG PS 0, median age 62 years. Child-Pugh (CP) was A in 5 and B7 in 1pt. Median tumour size was 4cm, and median number of lesions was 2. All-grade adverse events potentially related to treatment (tx) occurred in 50% of pts including diarrhoea (n=1, G3), skin rash (n=2, G2), infusion reaction (n=1, G2) and adrenal insufficiency (n=1, G2). Pembro yielded no synergistic toxicity with TACE and no DLTs were reported. At data cut-off, tx was ongoing for 3 pts with a median duration of tx of 2.8 months. Of the 4 radiologically evaluable patients, 3 had stable disease on pembro, 1 had progressive disease. Cause of withdrawal included disease progression/death (n=2) and worsening liver failure in the CP B7pt, non tx-related (n=1). Updated data from an expanded pt cohort will be shown and efficacy data will be correlated with T-cell responses to recognized tumor-associated antigens, tumour-infiltrating lymphocyte profiling and stool bacterial metagenomics. Conclusions The TACE+pembro combination had a tolerable safety profile with no evidence of synergistic toxicity. Alongside emerging efficacy data, this encourages the clinical development of the combination in CP A pts. Clinical trial identification NCT03397654. Legal entity responsible for the study Imperial College London. Funding Merck Sharp & Dohme. Disclosure D.J. Pinato: Research grant / Funding (self), Funder of the clinical study presented: MSD; Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): ViiV Healthcare; Honoraria (self), Travel / Accommodation / Expenses: Bayer. All other authors have declared no conflicts of interest.

To avoid liver insufficiency following major hepatic resection, portal vein embolisation (PVE) is used to induce liver hypertrophy pre-operatively. Associating liver partition with portal vein ligation for staged hepatectomy assisted with radiofrequency (RALPPS) was introduced as an alternative method. A randomized controlled trial comparing PVE with RALPPS for the pre-operative manipulation of liver volume in patients with a future liver remnant volume (FLRV) &le, 25% (or &le, 35% if receiving preoperative chemotherapy) was conducted. The primary endpoint was increase in size of the FLRV. The secondary endpoints were length of time taken for the volume gain, morbidity, operation length and post-operative liver function. Between July 2015 and October 2017, 57 patients were randomised to RALPPS (n = 29) and PVE (n = 28). The mean percentage of increase in the FLRV was 80.7 &plusmn, 13.7% after a median 20 days following RALPPS compared to 18.4 &plusmn, 9.8% after 35 days (p &lt, 0.001) following PVE. Twenty-four patients after RALPPS and 21 after PVE underwent stage-2 operation. Final resection was achieved in 92.3% and 66.6% patients in RALPPS and PVE, respectively (p = 0.007). There was no difference in morbidity, and one 30-day mortality after RALPPS (p = 0.991) was reported. RALPPS is more effective than PVE in increasing FLRV and the number of patients for surgical resection.

The ability to operate flexibly is critical for the future implementation of carbon capture and storage (CCS) in thermal power plants. A dynamic test campaign examines the response of a CO2 absorption/desorption pilot-scale plant to realistic changes in flue gas flow rates and steam supply, representative of the operation of a Natural gas combined cycle (NGCC) plant fitted with post-combustion capture. Five scenarios, demonstrating the operational flexibility that is likely to be encountered in an energy market with significant penetration from intermittent renewables, are presented, with 30% monoethanolamine (MEA) as the absorbing solvent. It complements a wider effort on dynamic modelling of these systems where a lack of dynamic plant data has been reported.The campaign focuses on analysing critical plant parameters of the response of the pilot plant to a gas turbine shutdown, a gas turbine startup and three enhanced operational flexibility scenarios, including two for power output maximisation and one for frequency response with a rapid increase of steam supply to the reboiler. The campaign also demonstrates the use of continuous in situ solvent lean loading measurement with the use of a novel online continuous liquid sensor.It confirms that no significant barriers to flexible operation of amine post-combustion capture are found, although there remains scope for the improvement of plant response. Solvent inventory and circulation times are found to have a significant effect on capture rate during certain dynamic operations. A large solvent inventory increases total circulation times, which can result in additional time being required for the plant to return to steady state following a perturbation. The plant is forced to operate with a non-optimal capture rate while the solvent loading at the absorber inlet stabilises is identified as a potential impact.Use of interim solvent storage and continuous online measurement of solvent CO2 loading, combined with comprehensive knowledge of liquid circulation times and potential mixing effects, are suggested as methods for improving plant response to dynamic operation, thereby increasing CCS plant flexibility.

Background: Preoperative portal vein occlusion with either percutaneous portal vein embolization (PVE) or portal vein ligation is routinely used to induce liver hypertrophy prior to major liver resection in patients with hepatic malignancy. While this increases the future liver remnant, and hence the number of patients suitable for resection, recent evidence suggests that induction of liver hypertrophy preoperatively may promote tumor growth and increase recurrence rates. The aims of this current study were to evaluate the impact of PVE on hepatic recurrence rate and survival in patients with colorectal liver metastases (CRLM). Methods: The MEDLINE, EMBASE and Web of Science databases were searched to identify studies assessing the oncological outcomes of patients undergoing major liver resection for CRLM following PVE. Studies comparing patients undergoing one-stage liver resection with or without preoperative PVE were included. The primary outcome was postoperative hepatic recurrence (PHR), while secondary outcomes were 3- and 5-year overall survival (OS). Results: Of the 2131 studies identified, six non-randomized studies (n = 668) met the eligibility criteria, comparing outcomes of patients undergoing major liver resection with or without PVE (n = 182 and n = 486, respectively). No significant difference was observed in PHR (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.42–1.44), 3-year OS (OR 0.80; 95 % CI 0.56–1.14) or 5-year OS (OR 1.12; 95 % CI 0.40–3.11). Conclusions: PVE does not have any adverse effect on PHR or OS in patients undergoing major liver resection for CRLM. Further studies based on individual patient data are needed to provide definitive answers.

The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002. This is the first update since then and is based on a comprehensive review of the recent literature, including data from randomised controlled trials, systematic reviews, meta-analyses, cohort, prospective and retrospective studies.

Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 x 10(8) pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.

Preoperative portal vein embolization (PVE) is used clinically to prevent postoperative liver insufficiency. The current study examined the impact of portal vein embolization on liver resection.A comprehensive Medline search to identify all registered literature in the English language on portal vein embolization. Meta-analysis was performed to assess the result of PVE and its impact on major liver resection.A total of 75 publications met the search criteria but only 37 provided data sufficiently enough for analysis involving 1088 patients. The overall morbidity rate for PVE was 2.2% without mortality. Four weeks following PVE, 85% patients underwent the planned hepatectomy (n = 930). Twenty-three patients had transient liver failure following resection after PVE (2.5%) but 7 patients developed acute liver failure and died (0.8%). The reason for nonresection following PVE (n = 158, 15%) included inadequate hypertrophy of remnant liver (n = 18), severe progression of liver metastasis (n = 43), extrahepatic spread (n = 35), refusal to surgery (n = 1), poor general condition (n = 1), altered treatment to transcatheter artery embolization or chemotherapy (n = 24), complete remission after treatment with 3 cycles of fluoracil and interferon alpha in a patient with hepatocellular carcinoma (n = 1), incomplete pre- or postembolization scanning (n = 8). Of those who underwent laparotomy without resection, (n = 27) reasons included intraoperative finding of peritoneal dissemination (n = 15), portal node metastasis (n = 2), severe invasion of the tumor to the hepatic artery and portal vein (n = 1), and gross tumoral extension precluding curative resection (n = 9). Two techniques were used for portal vein embolization: percutaneous transhepatic portal embolization, (PTPE) and transileocolic portal embolization, (TIPE). The increase in remnant liver volume was much greater in PTPE than TIPE group (11.9% vs. 9.7%; P = 0.00001). However, the proportion of patients who underwent resection following PVE was 97% in TIPE and 88% PTPE, respectively (P =0.00001). Although there was no significant difference in patients who had major complications post-PVE, the rate for minor complications was significantly higher among patients who had PTPE (53.6% vs. 0%, P =0.0001).PVE is a safe and effective procedure in inducing liver hypertrophy to prevent postresection liver failure due to insufficient liver remnant.

Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34(+) adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long-term follow-up of these patients. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12-18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long-term follow-up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin increased only at 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.

Primary and secondary liver tumours are common malignancies that are being treated more aggressively nowadays than decades ago. Surgery is the most effective method of treatment but is only suitable for a minority of patients with well-defined and easily accessible tumours. Surgical resection is contraindicated in patients with massive involvement of the liver or in cases where the disease involves the confluence of vessels at the porta hepatis. These patients may benefit from a variety of ablative and embolic therapies including selective internal radiation therapy (SIRT) with Yttrium-90 microspheres. SIRT has been introduced in the 1980's but the technology has been refined and made more available only recently. The microspheres are injected directly into the hepatic arteries, through a trans-femoral angiographic approach, and are delivered selectively to tumours due to their preferential blood supply by hepatic arteries. SIRT can therefore target small volumes disease with a higher dose of radiation compared with external-beam radiation and is associated the relatively low toxicity and a good response irrespective of tumor origin. Assessment of response to therapy is best performed with metabolic imaging using (18)F-FDG PET scanning. Although it is not considered as a cure, it has been shown to improve quality of life and prolong survival, with the main cause of death being extra-hepatic spread. The technical and clinical demands of patient selection, treatment planning, administration, and clinical follow-up require an interdisciplinary team willing to work cooperatively to achieve the best result for the patient.

Introduction Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. Material and methods From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. Result Twenty-one patients (F = 11, M = 10; age range 40–75 years, mean = 58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary ( n = 10) and non-colorectal primaries ( n = 8), and primary liver tumours ( n = 3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2–2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks ( p = 0.01). The mean pre-treatment SUV was 12.2 ± 3.7 and the mean post-treatment SUV was 9.3 ± 3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127 ± 115 vs 75 ± 72 μ/l, p = 0.39). Complications were seen in 4 patients (19%) including radiation hepatitis ( n = 2), cholecystitis ( n = 1) and duodenal ulceration ( n = 1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). Conclusion SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Selective internal radiation therapy with 90Y microspheres (SIR spheres) is increasingly used in the treatment of extensive liver tumours. Careful selection and preparation of patients are necessary to avoid possible adverse effects. We aimed to evaluate the incidence and severity of adverse effects resulting from the administration of SIR spheres during therapy.Between June 2004 and August 2006, 21 patients (11 women and 10 men; age range 40-75 years; mean, 58 years) with a wide range of extensive liver tumours were treated with SIR spheres. The mean administered dose was 1.87 GBq (range 1.2-2.5 GBq). During the follow-up period of 26 months, all adverse effects were monitored and classified according to the National Cancer Institute criteria.Four patients had adverse effects: one case of cholecystitis followed by fibrosis and portal hypertension, one case of peptic ulceration and two cases of radiation hepatitis. All cases responded to appropriate therapy.Proper selection of patients and accurate interpretation of pre-treatment investigations are vital for minimizing adverse effects following therapy with SIR spheres. In our experience, all adverse effects were moderate with no life-threatening consequences.

School‐based education programmes on the prevention of sexual abuse may increase children's knowledge and protective behaviour but this does not necessarily reduce the number of incidents of abuse. The programmes should be seen as part of a community approach to prevent child sexual abuse. This is the conclusion of this Campbell/Cochrane systematic review of the best international research findings. Abstract Background Child sexual abuse is a significant problem that requires an effective means of prevention. Objectives To assess: if school‐based programmes are effective in improving knowledge about sexual abuse and self‐protective behaviours; whether participation results in an increase in disclosure of sexual abuse and/or produces any harm; knowledge retention and the effect of programme type or setting. Search strategy Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, CINAHL, Sociological Abstracts, Dissertation Abstracts and other databases using MESH headings and text words specific for child sexual assault and randomised controlled trials (RCTs) were conducted in August 2006. Selection criteria RCTs or quasi‐RCTs of school‐based interventions to prevent child sexual abuse compared with another intervention or no intervention. Data collection & analysis Meta‐analyses and sensitivity analysis, using two imputed intraclass correlation coefficients (ICC) (0.1, 0.2), were used for four outcomes: protective behaviours, questionnaire‐based knowledge, vignette‐based knowledge and disclosure of abuse. Meta‐analysis was not possible for retention of knowledge, likelihood of harm, or effect of programme type and setting. Main results Fifteen trials measuring knowledge and behaviour change as a result of school‐based child sexual abuse intervention programmes were included. Over half the studies in each initial meta‐analysis contained unit of analysis errors. For behaviour change, two studies had data suitable for meta‐analysis; results favoured intervention (OR 6.76, 95% CI 1.44, 31.84) with moderate heterogeneity (I2=56.0%) and did not change significantly when adjustments using intraclass coefficients were made. Nine studies were included in a meta‐analysis evaluating questionnaire‐based knowledge. An increase in knowledge was found (SMD 0.59; 0.44, 0.74, heterogeneity (I2=66.4%). When adjusted for an ICC of 0.1 and 0.2 the results were SMD 0.6 (0.45, 0.75) and 0.57 (0.44, 0.71) respectively. Heterogeneity decreased with increasing ICC. A meta‐analysis of four studies evaluating vignette‐based knowledge favoured intervention (SMD 0.37 (0.18, 0.55)) with low heterogeneity (I2=0.0%) and no significant change when ICC adjustments were made. Meta‐analysis of between‐group differences of reported disclosures did not show a statistically significant difference. Reviewers’ conclusions Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster‐adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3‐12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Selective internal radiation therapy (SIRT) with SIR spheres (90Y microspheres) is a treatment option for liver tumours in patients in whom other therapies are inappropriate or have failed. This study aims to assess the value of FDG PET in assessing the response to SIRT as compared to computed tomography (CT).Twenty-one patients (11 F, 10 M; age range 40-75 years, mean, 58 years) received SIR spheres at the Hammersmith Hospital. One patient received two treatments. Most patients had colorectal metastases (n=10), while the others (n=11) had liver metastasis from different primaries. The mean administered dose was 1.9 GBq (range, 1.2-2.5 GBq). Follow-up was done with FDG PET and CT at 6 weeks, and 6-monthly thereafter. Pre-therapy and post-therapy CT and PET scans were assessed visually (RECIST criteria for CT) and semi-quantitative for PET using the standardized uptake value (SUV).Eighty-six percent of patients showed decreased PET activity at 6 weeks while only 13% showed a partial response in the size of tumour on CT scan. The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7 (P=0.01). CT imaging showed progressive disease in 27% patients and stable liver disease in 60% patients. Based on FDG PET results one patient had surgery for down-staged tumour.FDG PET imaging is more sensitive than CT in the assessment of early response to SIR spheres, allowing clinicians to proceed with further therapeutic options.

A phase I study was performed to determine the safety and tolerability of injecting autologous CD34(+) cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34(+) cell population in granulocyte colony-stimulating factor (G-CSF)-mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34(+) stem cell population from the majority of the CD34(+) cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34(+) cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription-polymerase chain reaction-based gene expression analysis indicated that the adherent CD34(+) cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34(+) cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34(+) cell population contains cells with the potential to form hepatocyte-like cells, we gave G-CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.

Jaundice is a common condition which has a wide range of causes. Imaging plays a vital role in establishing the underlying aetiology and planning management. Image-guided interventional techniques are used for therapeutic procedures and for diagnostic purposes.

3507 Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate ( p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.

There are a number of challenges facing people in the last days of life who wish to receive care in their home environment. This includes timely access to medicines for symptom control.This article outlines the development of a concise list of core medicines that can provide symptom control in non-complex patients in the last days of life. The list is based on practical criteria including evidence of efficacy, affordability, the option for parenteral administration, availability on the Pharmaceutical Benefits Scheme and the doctors' emergency drug supply list.A list of core medicines can facilitate timely prescribing and supply of essential medicines for end-of-life symptom management. However, the development of this list should not replace planning and routine involvement of community resources. Multidisciplinary education strategies are needed to ensure that the core medicines list is utilised effectively by doctors, pharmacists and community nurses.

We report a 44-year-old woman who developed a fatal pulmonary embolus after uterine artery fibroid embolisation (UAE). Bilateral UAE was carried out through a single right-femoral artery puncture. The largest fibroid in the anterior fundal wall measured 4.5 cm, and the largest fibroid in the posterior fundal wall measured 6 cm. The appearances after UAE were satisfactory, and the procedure was apparently uneventful. No immediate complications were noted. The patient developed sudden-onset shortness of breath and went into cardiac arrest 19 h after the procedure. Postmortem autopsy confirmed that the cause of a death was a pulmonary embolism. To our knowledge this is the first reported case in the United Kingdom in which death occurred from a pulmonary embolus after UAE.