Search

Background Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS). Methods A systematic review was conducted to identify RCT’s reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA. Results Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12–93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR: 0.50, 95% CI: 0.19–1.31) and OS (HR: 0.41, 95% CI: 0.19–0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR: 0.21, 95% CI: 0.05–0.93). Conclusion This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.

Background Dextran 40 (D40) is a synthetic colloid with anticoagulant properties that is used instead of heparin after pancreas transplantation; however, there is a lack of evidence on which is more effective. Graft thrombosis and pancreatitis, which may be mediated through microthrombosis or macrothrombosis within the graft, remain significant complications after pancreas transplantation. We hypothesized that D40 reduces inflammation through its antithrombotic promicrocirculatory effects. We evaluated D40 compared to a heparin-based protocol by comparing postoperative complications and post-transplant levels of inflammation. Materials and Methods Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018. A total of 26 patients had been treated with the pre-dextran protocol and 37 had received D40. Postoperative complications and inflammatory markers (white cell count [WCC], C-reactive protein [CRP], and amylase) on postoperative days 1, 2, 3, and 7 were compared between groups. Potential confounders were also recorded. Results Patients in the D40 group had similar thrombosis rates but were less likely to have had graft loss as a result of thrombosis or substantial postoperative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3, and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders of cold ischemic time and donor age. Conclusions D40 appears to be as effective as intravenous heparin at preventing graft thrombosis after pancreas transplant and to confer a reduced risk for bleeding. It may also reduce postoperative inflammatory processes, leading to reduced graft pancreatitis.

Introduction The aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE). Materials and methods A Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included ‘watch and wait’, ‘transplantation’ (pre-, post and post (No HCC)), ‘resection’, ‘no HCC other’, ‘pharmacological management’ and ‘death’. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature. Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken. Results TheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options. Conclusions This study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and usually occurs in the context of chronic liver disease. Due to its increasing incidence and high mortality, HCC is a major public health concern. The improved prevention and treatment of chronic hepatitis infection, combined with the recent epidemic of the metabolic syndrome, has led to non-alcoholic fatty liver disease (NAFLD) becoming a rapidly growing cause of HCC. NAFLD is now the leading of cause of HCC in many developed countries and is predicted to become much more common worldwide. The rise of NAFLD presents major challenges for the screening, diagnosis and treatment of HCC. Current HCC screening programmes are inadequate because they only screen for HCC in patients with cirrhosis, whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis. Consequently, NAFLD patients often present with a more advanced stage of HCC, with a poorer prognosis. NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies, including type 2 diabetes mellitus (T2DM), obesity, cardiovascular disease and cerebrovascular disease. This limits the use of curative treatments such as liver resection and orthotopic liver transplantation (OLT). Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes, overall long-term survival is comparable to HCC of other etiologies. This highlights the importance of careful patient selection, pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment. Careful consideration is also important for non-surgical treatments, although the evidence supporting treatment selection is frequently lacking, as these patients tend to be poorly represented in clinical trials. Locoregional therapies such as percutaneous ablation and transarterial chemoembolization (TACE) may be less well tolerated and less effective in NAFLD patients with obesity or diabetes. The tyrosine kinase inhibitor sorafenib may also be less effective. This review highlights how international guidelines, for which NAFLD traditionally has made up a small part of the evidence base, may not be appropriate for all NAFLD-HCC patients. Further studies are needed to evaluate the effectiveness of current treatment strategies in NAFLD-HCC. Future guidelines need to reflect the changing landscape of HCC, by making specific recommendations for the management of NAFLD-HCC.

Background: Theoretical advantages of robotic surgery compared to conventional laparoscopic surgery include improved instrument dexterity, 3D visualization, and better ergonomics. This systematic review and meta-analysis aimed to determine advantages of robotic surgery over laparoscopic surgery in patients undergoing liver resections. Method: A systematic literature search was conducted for studies comparing robotic assisted or totally laparoscopic liver resection. Meta-analysis of intraoperative (operative time, blood loss, transfusion rate, conversion rate), oncological (R0 resection rates), and postoperative (bile leak, surgical site infection, pulmonary complications, 30-day and 90-day mortality, length of stay, 90-day readmission and reoperation rates) outcomes was performed using a random effects model. Result: Twenty-six non-randomized studies including 2630 patients (950 robotic and 1680 laparoscopic) were included, of which 20% had major robotic liver resection and 14% had major laparoscopic liver resection. Intraoperatively, robotic liver resection was associated with significantly less blood loss (mean: 286 vs 301 mL, p Conclusions: Robotic liver resection appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomized trial comparing both techniques is needed.

The role of adjuvant therapy for biliary tract cancer is not clearly defined with conflicting results demonstrated across nonrandomized and randomized studies. We report a systematic review and meta-analysis to delineate the effect of AT on overall survival.Eligible studies were identified from MEDLINE, EMBASE, Cochrane and PubMed. Studies comparing adjuvant chemotherapy or chemoradiotherapy after curative-intent surgery with curative surgery only for biliary tract cancer were included. Data pertaining to tumours of the gallbladder and bile ducts were included. The primary outcome assessed was overall survival. Random-effects meta-analysis was performed, as well as pooling of unadjusted Kaplan-Meier curve data.35 studies involving 42,917 patients were analysed. There was a significant improvement in overall survival with any adjuvant therapy after surgery compared with surgery only (HR 0.74; 95% CI, 0.67 to 0.83; P 0.001). There was a significant benefit for adjuvant therapy in those with margin positive surgery (RR, 0.83; 95% CI, 0.77 to 0.91; P0.001) and node-positive disease (RR 0.82; 95% CI 0.76 to 0.89; P 0.001) CONCLUSION: Our review advocates the use of adjuvant therapy in bile duct cancer after curative intent resection. Further prospective studies are needed to determine the optimal regime and timing of an adjuvant approach.

Background Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique. This systematic review and network meta-analysis aims to characterise and identify the best reported technique for elective parenchymal liver transection based on published randomised controlled trials (RCT's). Methods A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Central to identify RCT's up to 5th June 2019 that examined parenchymal transection for liver resection. Data including study characteristics and outcomes including intraoperative (blood loss, operating time) and postoperative measures (overall and major complications, bile leaks) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. Results This study identified 22 RCT's involving 2360 patients reporting ten parenchymal transection techniques. Bipolar cautery has lower blood loss and shorter operating time than stapler (mean difference: 85 mL; 22min) and Tissue Link (mean difference: 66 mL; 29min). Bipolar cautery was ranked first for blood loss and operating time followed by stapler and TissueLink. Harmonic scalpel is associated with lower overall complications than Hydrojet (Odds ratio (OR): 0.48), BiClamp forceps (OR: 0.46) and clamp crushing (OR: 0.41). Conclusion Bipolar cautery techniques appear to best at reducing blood loss and associated with shortest operating time. In contrast, Harmonic scalpel appears best for overall and major complications. Given the paucity of data and selective outcome reporting, it is still hard to identify what is the best technique for liver resection. Therefore, further high-quality large-scale RCT's are still needed.

Introduction: Laparoscopic distal pancreatectomy (LDP) has potential advantages over its open equivalent open distal pancreatectomy (ODP) for pancreatic disease in the neck, body and tail. Within the United Kingdom (UK), there has been no previous experience describing the role of robotic distal pancreatectomy (RDP). This study evaluated differences between ODP, LDP and RDP. Methods: Patients undergoing distal pancreatectomy performed in the Department of Hepatobiliary and Pancreatic Surgery at the Freeman Hospital between September 2007 and December 2018 were included from a prospectively maintained database. The primary outcome measure was length of hospital stay, and the secondary outcome measures were complication rates graded according to the Clavien–Dindo classification. Results: Of the 125 patients, the median age was 61 years and 46% were male. Patients undergoing RDP (n = 40) had higher American Society of Anesthesiologists grading III compared to ODP (n = 38) and LDP (n = 47) (57% vs. 37% vs. 38%, P = 0.02). RDP had a slightly lower but not significant conversion rate (10% vs. 13%, P = 0.084), less blood loss (median: 0 vs. 250 ml, P < 0.001) and a higher rate of splenic preservation (30% vs. 2%, P < 0.001) and shorter operative time, once docking time excluded (284 vs. 300 min, P < 0.001) compared to LDP. RDP had a higher R0 resection rate than ODP and LDP (79% vs. 47% vs. 71%, P = 0.078) for neoplasms. RDP was associated with significantly shorter hospital stay than LDP and ODP (8 vs. 9 vs. 10 days, P = 0.001). While there was no significant different in overall complications across the groups, RDP was associated with lower rates of Grade C pancreatic fistula than ODP and LDP (2% vs. 5% vs. 6%, P = 0.194). Conclusion: Minimally invasive pancreatic resection offers potential advantages over ODP, with a trend showing RDP to be marginally superior when compared to conventional LDP, but it is accepted that that this is likely to be at greater expense compared to the other current techniques.

Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers.Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019.The retrieval rate for deceased donor livers (71% vs. 54%; P .0001) and conversion from offer to completed transplant (63% vs. 48%; P .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort.We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Objectives Pancreas transplant is a major intraabdominal operation, and in most cases the graft is placed in the rightiliac fossa. At our center, preemptive appendicectomy is performed at the time of pancreas transplant to prevent any future risk in a complex transplant patient. The aim of this study was to review all histology reports from the removed appendices. Materials and methods The histology reports from all incidental appendicectomies performed at pancreas transplant were reviewed. Results Between January 2001 and June 2016, 107 pancreas transplants were performed (86 simultaneous pancreas and kidney transplants, 11 pancreas after kidney transplants, and 10 pancreas transplants alone), and 65 appendix histology reports were available from this patient group. All were preemptive appendicectomies as none of the patients had symptoms to suggest acute appendicitis. Of the 65 appendix histologies, 43 (66.2%) were reported as normal. Twenty specimens (30.8%) showed fibrosis consistent with previous inflammation of the appendix, and 12 specimens (18.5%) showed fecal material in the lumen (1 due to an obstructing fecalith and another 2 showing luminal distension with feces). Three specimens (4.6%) showed lymphoid hyperplasia. There were 5 (7.7 %) unexpected findings upon histology. In review of histology reports, 1 patient had a 1.1-mm carcinoid tumor in an otherwise normal appendix, 1 had an Enterobius species worm infestation, 1 had focal endometriosis, 1 had crypt abscesses suggestive of inflammatory bowel disease, 1 had a metaplastic polyp, and 1 had melanosis coli of unknown clinical significance. There were no cases of overt acute appendicitis. No patients experienced a complication as a direct result of their appendicectomy. Conclusions A policy ofroutine appendicectomy atthe time of pancreas transplant appears to be justified and safe.

Background The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). Methods A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Results Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Conclusions Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.

Data supporting routine use of adjuvant chemotherapy (AC) compared to no AC (noAC) for perihilar cholangiocarcinoma (hCCA) is unclear. This study aimed to determine whether AC improves long-term survival following resection for hCCA.Patients receiving resection for hCCA followed by AC or no AC from 2010 to 2016 were identified from the National Cancer Database (NCDB). Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival.Of 924 (56%) noAC and 719 (44%) AC, 320 noAC and 320 AC patients remained after PSM. After matching, AC was associated with improved survival (median: 28.2 vs 19.9 months, p 0.001), which remained after multivariable adjustment (HR: 0.61, CIAC following resection for hCCA was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings suggest incorporation of AC into multimodality therapy for hCCA in all cases, where appropriate.

Introduction: Minimally invasive liver surgery for hepatocellular carcinoma has gained widespread interest as an alternative to conventional open liver surgery. However, long-term survival benefits of this approach seem unclear. This meta-analysis was conducted to investigate long-term survival following minimally invasive liver surgery. Method: A systematic review was performed to identify studies comparing long-term survival after minimally invasive liver surgery and open liver surgery until January 2020. The I2 test was used to test for statistical heterogeneity and publication bias was assessed using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study factors (region, design), annual center volume, patient factors (American Society of Anesthesiologists (ASA) grade, gender, age, body mass index, cirrhosis, tumor size, and number), and resection extent. Sensitivity analyses were performed on studies by study year, region, annual center volume, and resection type. Result: The review identified 50 relevant studies including 13,731 patients undergoing liver resection for hepatocellular carcinoma of which 4071 (25.8%) underwent minimally invasive liver surgery. Pooled analysis revealed similar all-cause (odds ratio: 0.83, 95% confidence interval: 0.70–1.11, p = 0.3) and disease-specific (odds ratio: 0.93, 95% confidence interval: 0.80–1.09, p = 0.4) 5-year mortality after minimally invasive liver surgery compared with open liver surgery. Sensitivity analysis of published studies from 2010 to 2019 demonstrated a significantly lower disease-specific 3-year mortality (odds ratio: 0.75, 95% confidence interval: 0.59–0.96, p = 0.022) and all-cause 5-year mortality (odds ratio: 0.63, 95% confidence interval: 0.50–0.81, p = 0.002). Meta-regression identified no confounding factors in all analyses. Conclusions: Improvement in minimally invasive liver surgery techniques over the past decade appears to demonstrate superior disease-specific mortality with minimally invasive liver surgery compared to open liver surgery. Therefore, minimally invasive liver surgery can be recommended as an alternative surgical approach for hepatocellular carcinoma.

Simple Summary This literature review shows preliminary evidence to suggest that electroporation, the use of electricity to cause the death of cells around the tumour, may be associated with an improved survival and complete resection rates following pancreatic surgery for higher stage pancreatic cancer. However, one in five patients have a complication from the procedure that alters their normal course in hospital. Moreover, the number of patients who underwent this technique is small and further data is needed to support the preliminary evidence. The results therefore should be interpreted with caution. Abstract The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.

Purpose To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). Methods A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). Results Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6–18.1). Overall survival was 8.7 months (95% CI, 5.3–12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6–3.1), and LPFS was 3.1 months (95% CI, 1.3–4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1–2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. Conclusions Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.

Precision cut liver slices (PCLSs) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono- or co-cultures. The aim of this study was to develop a bioreactor system to increase the healthy life span of PCLSs and model fibrogenesis. PCLSs were generated from normal rat or human liver, or fibrotic rat liver, and cultured in our bioreactor. PCLS function was quantified by albumin enzyme-linked immunosorbent assay (ELISA). Fibrosis was induced in PCLSs by transforming growth factor beta 1 (TGFβ1) and platelet-derived growth factor (PDGFββ) stimulation ± therapy. Fibrosis was assessed by gene expression, picrosirius red, and α-smooth muscle actin staining, hydroxyproline assay, and soluble ELISAs. Bioreactor-cultured PCLSs are viable, maintaining tissue structure, metabolic activity, and stable albumin secretion for up to 6 days under normoxic culture conditions. Conversely, standard static transwell-cultured PCLSs rapidly deteriorate, and albumin secretion is significantly impaired by 48 hours. TGFβ1/PDGFββ stimulation of rat or human PCLSs induced fibrogenic gene expression, release of extracellular matrix proteins, activation of hepatic myofibroblasts, and histological fibrosis. Fibrogenesis slowly progresses over 6 days in cultured fibrotic rat PCLSs without exogenous challenge. Activin receptor-like kinase 5 (Alk5) inhibitor (Alk5i), nintedanib, and obeticholic acid therapy limited fibrogenesis in TGFβ1/PDGFββ-stimulated PCLSs, and Alk5i blunted progression of fibrosis in fibrotic PCLS. Conclusion: We describe a bioreactor technology that maintains functional PCLS cultures for 6 days. Bioreactor-cultured PCLSs can be successfully used to model fibrogenesis and demonstrate efficacy of antifibrotic therapies. ispartof: HEPATOLOGY vol:70 issue:4 pages:1377-1391 ispartof: location:United States status: published

Hilar cholangiocarcinoma (HCCA) arises from the confluence of the common hepatic duct and has a poor prognosis. If resectable, an extended left (eLH) or right hemihepatectomy (eRH) is usually required to provide oncological clearance. We reviewed outcomes for patients with HCCA managed at our centre. Electronic records of patients referred to our centre for HCCA were retrospectively reviewed. The Kaplan–Meier method was used to estimate overall survival (OS) with the log rank test used for significance (p 0.05). Patients undergoing an eLH for HCCA have significantly better long-term outcomes compared to those undergoing eRH, independent of other pathological variables. The functional liver remnant (FLR) is usually smaller following eRH, resulting in a higher risk of post-operative liver failure. Combining CT volumetry with PVE may result in better prediction and optimisation of the FLR in the context of eRH for HCCA. An extended left hemihepatectomy is an independent predictor of survival; investigation into the precise interaction between left- and right-sided resections and pre- and post-embolization liver volume is warranted.

IntroductionSelective internal radiotherapy (SIRT) with yttrium-90 (Y-90) is an intra-arterial therapy for hepatic malignancy in patients who are unsuitable for surgical resection. This treatment is considered palliative, although some patients can demonstrate a response that is adequate to facilitate surgical resection with curative intent.MethodsAll patients who underwent liver resection post SIRT were reviewed. Data gathered included patient demographics, tumor type, surgical details, and post-operative outcomes.ResultsTwelve patients underwent SIRT followed by liver resection (7 males and 5 females). Pathologies were hepatocellular carcinoma (n = 5), metastatic colorectal cancer (n = 5), and neuroendocrine tumor (n = 2). Lesional response (size, volume, and RECIST (response evaluation criteria in solid tumors)) was calculated and where appropriate functional liver remnant (FLR) is presented. Mean FLR increase was 264cm3(range − 123 to 909), and all cases demonstrated a partial response according to RECIST with a mean largest lesion volume reduction of 475cm3(range 14–1632). No post-SIRT complications were noted. Hepatectomy occurred at a mean of 322 days from SIRT treatment. Ninety-day morbidity was 67% (n = 6), complications post-surgery were analyzed according to the Clavien-Dindo classification scale; a total of 15 events occurred in 6 patients. Ninety-day mortality of 11% (n = 1).ConclusionIn selected cases, liver resection is possible post SIRT. As this can represent a potentially curative option, it is important to reconsider resection in the follow-up of patients undergoing SIRT. Post-operative complications are noted following major and extended liver resection. Therefore, further studies are needed to improve patient selection.

Aims Patients with chemotherapy-refractory colorectal cancer liver metastases have limited therapeutic options. Selective internal radiation therapy (SIRT) delivers yttrium 90 microspheres as a minimally invasive procedure. This prospective, single-arm, observational, service-evaluation study was part of National Health Service England Commissioning through Evaluation. Methods Patients eligible for treatment had histologically confirmed carcinoma with liver-only/liver-dominant metastases with clinical progression during or following oxaliplatin-based and irinotecan-based chemotherapy. All patients received SIRT plus standard of care. The primary outcome was overall survival; secondary outcomes included safety, progression-free survival (PFS) and liver-specific PFS (LPFS). Results Between December 2013 and March 2017, 399 patients were treated in 10 centres with a median follow-up of 14.3 months (95% confidence interval 9.2–19.4). The median overall survival was 7.6 months (95% confidence interval 6.9–8.3). The median PFS and LPFS were 3.0 months (95% confidence interval 2.8–3.1) and 3.7 months (95% confidence interval 3.2–4.3), respectively. During the follow-up period, 143 patients experienced an adverse event and 8% of the events were grade 3. Conclusion Survival estimates from this pragmatic study show clinical outcomes attainable in the National Health Service comparable with previously published data. This study shows the value of a registry-based commissioning model to aid national commissioning decisions for highly specialist cancer treatments.

OBJECTIVES Induction immunosuppression for simultaneous pancreas-kidney transplant has helped reduce graft loss due to early rejection. Both thymoglobulin and interleukin 2 receptor antagonists are the most commonly used induction agents; however, some high-volume centers prefer alemtuzumab.Thisnetwork meta-analysis aimedto compare differentinductionregimens for simultaneouspancreaskidney transplantin terms ofbothpancreas and patient graft survival, as well to assess acute rejection. MATERIALS AND METHODS A systematic review was conducted to identify randomized clinical trials up to October 31, 2019, that examined induction regimens for simultaneous pancreas-kidney transplant. Study characteristics, postoperative data (patient, pancreas, and kidney graft survival), complications (eg, bleeding), infection rates, and malignancy rates were extracted. We compared all regimens using randomeffects network meta-analyses to maintain randomization within trials. RESULTS This study identified 7 randomized clinical trials that involved 536 patients, which reported 5 induction regimens. These regimens included antithymocyte globulin (97 patients), alemtuzumab (42 patients), 2 doses (113 patients) or 5 doses (164 patients) of daclizumab, and no induction therapy (120 patients). In the network meta-analysis, a regimen with 2 doses of daclizumab was consistently ranked first for patient survival and kidney and pancreas graft survival. In contrast, alemtuzumab was ranked best for acute rejection (both pancreas and kidney). Rates of majorinfection (ie, cytomegalovirus) and malignancy were reported in 3 studies, precluding a reliable analysis. CONCLUSIONS Daclizumab with 2 doses, given before simultaneous pancreas-kidney transplant, was associated with the best rates of patient and graft survival. Despite the recent withdrawal of daclizumab, an alternative anti-interleukin 2 induction regimen (basiliximab) has demonstrated promising results in nonrandomized series, warranting that further highquality large-scale randomized clinical trials are still needed.

Introduction The UK has been severely affected by the COVID-19 pandemic. The impact on the adult population has been disproportionately higher when compared to children with consequent challenges to organ donation and liver transplantation (LT). Across the three UK paediatric liver centres there has only been a very small number of patients who tested positive for COVID-19 and all made a speedy and full recovery. We report here the response during the pandemic across the 3 paediatric LT centres. Methods A series of nationally agreed policy changes affecting the liver procurement, listing and transplant process were agreed during regular meetings with LT centre directors and NHSE. Actions at a local and national level were agreed to protect and maintain the paediatric LT programmes. Data were collected from 27/03/20 until 26/11/20 and compared with same time period for the years 2016–19. Results During the study period, there was a significant reduction in the adult population in the mean number of weekly liver offers, donors and LTs compared to before the pandemic with signs of recovery between the 1st and 2nd UK lockdown periods (figure 1). More specifically the number of livers offered nationally was reduced from an average 30–40/week to only Overall, 65–80 paediatric LTs are performed annually across the UK’s 3 paediatric centres. From March-November 2020 there were 58(82%) elective and 13(18%) super urgent (acute liver failure & hepatoblastoma) paediatric LTs performed. Donor Brain Dead (DBD) and Donor Cardiac Dead (DCDC) LTs were 54(76%) and 3(4%), respectively. Living related LT (LRLT) programme was sustained comprising 20% of LTs performed. The number of paediatric LTs performed during the pandemic was comparable to those performed yearly since 2016. The number of LT per paediatric centre for King’s College Hospital (KCH), Birmingham Children’s Hospital (BCH) and Leeds Liver Unit were 40 (56%), 15(21%) and 16(23%), respectively with excellent outcome. A 15-year-old girl from KCH diagnosed with Wilson disease presented with liver failure and became COVID-19 positive whilst listed. She underwent LT soon after becoming COVID-19 negative. No perioperative mortality was reported with excellent outcome so far in all. Conclusion The current COVID-19 pandemic had a significant impact on the UK adult LT programme. The paediatric programme LT was preserved despite a decrease in organ offering and retrieval nationally plus limitations on adult intensive care resources at a regional level. Overall, paediatric LT outcome remained very good.

Introduction Dextran 40 (D40) is a synthetic colloid with anticoagulant properties, which is commonly used instead of heparin following pancreas transplantation, however there is a lack of evidence over which is more effective. Graft thrombosis and pancreatitis, which may be mediated through micro or macrothrombosis within the graft, remain significant complications following pancreas transplantation. We hypothesised that D40 reduces inflammation through its antithrombotic pro-microcirculatory effects. We aimed to evaluate D40 compared to a heparin-based protocol by comparing post-operative complications and post-transplant levels of inflammation. Method Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018 – 26 patients had been treated with the pre-Dextran protocol and 37 had received D40. Post-operative complications and inflammatory markers (WCC, CRP and amylase) on post-operative days 1, 2, 3 and 7 were compared between the two groups. Potential confounders were also recorded. Result Patients in the D40 group had similar thrombosis rates but were less likely to have had substantial post-operative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3 and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders - cold ischaemic time and donor age. Conclusion D40 appears to be as effective as IV heparin at preventing graft thrombosis following pancreas transplant, and to confer a reduced risk of bleeding. It may also reduce post-operative inflammatory processes, leading to reduced graft pancreatitis. Take-home message Using Dextran 40 as an anticoagulant after pancreas transplantation is as effective as IV heparin at preventing graft thromboses and has a reduced risk of bleeding.

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.

The protocol is out of date and does not meet the current methodological standards of Cochrane. Withdrawn by Cochrane Colorectal group, currently no plans to revise/republish.

The recent SARS-CoV-2 (COVID-19) pandemic has led to significant disruptions to healthcare delivery, including organ transplantation. In the UK, of 6136 patients on an active transplant list 3.8 per cent tested positive for COVID-19 and 11.0 per cent of these have died. Of 2084 transplants performed in the UK during 2020, 3.4 per cent of patients tested positive but only 0.5 per cent have died1. Most would agree that, for certain groups, risk is higher whilst on a waiting list rather than after a successful transplant. We accept that figures may vary because of the frequency and density of testing. Although the impact of COVID-19 on liver2,3 and renal4 transplant activity is reported, it remains less clear for pancreas transplantation. Of 1757 simultaneous pancreas–kidney recipients in the UK with a functioning graft 23 (1.3 per cent) have developed COVID-19 and only five have died1. An online survey covering key areas for pancreas transplant services was developed and disseminated via the World Pancreas Transplant Guidelines Group between May and July 2020. A total of 28 respondents from 28 centres and 16 countries spanning four continents completed the online survey. One further respondent from the USA was unable to complete the questionnaire as during the COVID-19 pandemic his centre had temporarily ceased transplantation altogether. Most respondents were transplant surgeons (15, 54 per cent), followed by hepatobiliary, pancreatic and transplant surgeons (8, 29 per cent), and general surgeons (5, 18 per cent). The majority worked in an academic centre (26, 93 per cent), with 50 per cent having between 501 and 1000 hospital beds. Eleven of the 28 centres (39 per cent) had between 51 and 100 hospital ICU beds. Patients with COVID-19 were already in 25 (89 per cent) of all hospitals, with four centres (14 per cent) having more than 100 inpatients with COVID-19. The majority of centres were at CRITCON level 0, ‘business as usual’ (10 centres, 36 per cent), followed by CRITCON level 1, ‘normal winter’ (8 centres, 29 per cent), and CRITCON level 2, ‘unprecedented’ (7 centres, 25 per cent)5. This survey highlights the significant reduction in pancreas transplant referrals, which was in excess of 75 per cent in nearly 40 per cent of the 28 centres. There had been a decrease in utilization of both donation after circulatory death (DCD) and donation after brain death (DBD) donors, from 46.4 to 7.1 per cent. In the UK during the months of March and April 2020, total organ retrievals were down by over 95 per cent. Both donors and recipients were screened for COVID-19, with 26 of the 28 centres (93 per cent) opting for polymerase chain reaction (PCR) swab testing, and nine centres (33 per cent) also using CT. For donors testing positive, 10 centres (36 per cent) never used the pancreas, and remaining 18 centres waited to use a donor pancreas either 14 days (1 centre, 4 per cent), 14–28 days (2 centres, 7 per cent), or more than 28 days (15 centres, 54 per cent) after a positive test. The median number of annual pancreas transplants performed in responding centres was 20 (range 2–70). There was a reduction in transplants between March and April 2020 compared with the same period during 2019, from a median of 4 (1–12) to 2 (0–8) respectively. The majority of centres (21, 75 per cent) were still performing pancreas transplants in their usual hospital theatre, but seven centres (25 per cent) performed transplants in the same hospital but a different theatre. Prioritization of patients was still based on waiting time and need for dialysis. After surgery, 16 (57 per cent) of the 28 centres sent transplant patients to a clean ICU, followed by transplant wards or suitable alternatives to ICU (7 centres, 25 per cent), or to a dirty/contaminated ICU (1 centre, 4 per cent). With respect to induction therapy, there were reductions in standard-dose antithymocyte globulin (ATG) (from 18 (64 per cent) to 12 (43 per cent) of the 28 centres) and standard-dose alemtuzumab (from 6 (21 per cent) to 3 (11 per cent) centres), and an increase in dose-reduced ATG (from 4 (14 per cent) to 5 (18 per cent) centres) and basiliximab (from 4 (14 per cent) to 7 (25 per cent) centres). There were no changes to maintenance therapy, which largely included tacrolimus, mycophenolate mofetil, prednisolone and sirolimus. Finally, of surgeons who tested positive for COVID-19, 29 per cent (8/28) were symptomatic and 61 per cent (17/28) were asymptomatic. Furthermore, 23 surgeons (82 per cent) were not redeployed but remained working either at home (4, 14 per cent), transferred to medical wards (2, 7 per cent) or HDU/ICU (1, 4 per cent), or into management (1, 4 per cent). This international survey demonstrates a high level of variation in availability of pancreas transplant services during the COVID-19 pandemic. Given the fall in activity and the added risk of COVID-19, waiting list mortality will inevitably increase. These data highlight the management challenges and practice variations in caring for these complex patients. Dissemination of data from this survey will improve our understanding of current international clinical practice during the pandemic. This study has identified the need for clear and consistent national or international recommendations to ensure a standard level of care for all patients awaiting pancreas transplant. Unfortunately, agreement on recommendations could prove challenging given the variation in how governments have decided to deal with the pandemic in their individual countries. Fil: Kamarajah, S. K.. Freeman Hospital; Reino Unido Fil: Arbogast, H.. Freeman Hospital; Reino Unido Fil: Berney, T.. Freeman Hospital; Reino Unido Fil: Boggi, U.. Freeman Hospital; Reino Unido Fil: Branchereau, J.. Freeman Hospital; Reino Unido Fil: Socci, C.. Freeman Hospital; Reino Unido Fil: Casanova, D.. Freeman Hospital; Reino Unido Fil: Cooper, M.. Freeman Hospital; Reino Unido Fil: Drage, M.. Freeman Hospital; Reino Unido Fil: Elker, D.. Freeman Hospital; Reino Unido Fil: Ferrer, J.. Freeman Hospital; Reino Unido Fil: Furian, L.. Freeman Hospital; Reino Unido Fil: Gruessner, R.. Freeman Hospital; Reino Unido Fil: Harper, S.. Freeman Hospital; Reino Unido Fil: Kwiatkowski, A.. Freeman Hospital; Reino Unido Fil: Kenmochi, T.. Freeman Hospital; Reino Unido Fil: Manas, D.. Freeman Hospital; Reino Unido Fil: Morelon, E.. Freeman Hospital; Reino Unido Fil: Odorico, J.. Freeman Hospital; Reino Unido Fil: Oellinger, R.. Freeman Hospital; Reino Unido Fil: Oniscu, G.. Freeman Hospital; Reino Unido Fil: Perosa, M.. Freeman Hospital; Reino Unido Fil: Saudek, F.. Freeman Hospital; Reino Unido Fil: Scalea, J.. Freeman Hospital; Reino Unido Fil: Schenker, P.. Freeman Hospital; Reino Unido Fil: Stratta, Ricardo Ruben. Freeman Hospital; Reino Unido Fil: Vistulo, F.. Freeman Hospital; Reino Unido Fil: Uva, Pablo Daniel. Freeman Hospital; Reino Unido. Instituto de Nefrología de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: White, S.A.. Freeman Hospital; Reino Unido

The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p

Background Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM. Methods A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed. Results One randomized and nine observational studies including 2232 patients: 1551 (69%) comprised the Surg cohort, 521 (23%) the interventional NSurg group and 160 (7%) the observational NSurg group. A significantly higher overall survival (OS) was observed when Surg was compared to interventional NSurg at 1 year (Surg 88%, 310/352; interventional NSurg 64%, 245/383; odds ratio (OR) 2.77 (confidence interval (CI) 1.94-3.97), P = 0.001), at 3 years (Surg 59%, 857/1444; interventional NSurg 26%, 138/521; OR 2.61 (CI 1.65-4.15), P = 0.002), at 5 years (Surg 47%, 533/1144; interventional NSurg 23%, 45/196; OR 3.24 (CI 1.42-7.39), P = 0.009) and at 10 years (Surg 27%, 306/1122; interventional NSurg 1%, 2/168; OR 15.64 (CI 1.87-130.76), P = 0.031). Surg was associated with a greater OS than observational NSurg at only 1 year (Surg 92%, 98/107; observational NSurg 83%, 133/160; OR 6.69 (CI 1.33-33.58), P = 0.037) and was similar to observational NSurg at all other OS time points. Comparable survival was observed among Surg and overall NSurg cohorts at 3- and 5-year survival in articles published within the last 3 years. Conclusions Recent evidence suggests comparable survival with Surg and NSurg modalities for CRLM, contrasting to early evidence where Surg had an improved survival. Significant selection bias contributes to this finding, prompting the need for high powered randomized controlled trials and registry data.

BACKGROUND Early vascular complications following pancreatic transplantation are not uncommon (3%-8%). Typically, cross-sectional imaging is requested in response to clinical change. We instituted a change in protocol to request imaging pre-emptively to identify patients with thrombotic complications. METHODS In 2013, protocol computer tomography angiography (CTA) at days 3-5 and day 10 following pancreas transplantation was introduced. A retrospective analysis of all pancreas transplants performed at our institution from January 2001 to May 2019 was undertaken. RESULTS A total of 115 patients received pancreas transplants during this time period. A total of 78 received pancreas transplant without routine CTA and 37 patients with the new protocol. Following the change in protocol, we detected a high number of subclinical thromboses (41.7%). There was a significant decrease in invasive intervention for thrombosis (78.6% before vs 30.8% after, p = .02), and graft survival was significantly higher (61.5% before vs 86.1% after, p = .04). There was also a significant reduction in the number of graft failures (all-cause) where thrombosis was present (23.4% before vs 5.6% after, p = .02). Patient survival was unaffected (p = .48). CONCLUSIONS Implementation of early protocol CTA identifies a large number of patients with subclinical graft thromboses that are more amenable to conservative management and significantly reduces the requirement for invasive intervention.

Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory-confirmed SARS-CoV-2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow-up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case-mix. One hundred ninety-seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS-CoV-2. Mortality after testing positive for SARS-CoV-2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS-CoV-2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS-CoV-2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.

Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-β1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel-Pfkfb3 axis has potential for therapeutic applications in fibrotic disease. ispartof: NATURE METABOLISM vol:2 issue:11 ispartof: location:Germany status: published

Aim Irreversible electroporation (IRE) is a non-thermal ablative option in patients unsuitable for standard thermal ablation, due to its potential to preserve collagenous structures (vessels and ducts) and a reduced susceptibility to heat sink effects. In this series from two large tertiary referral hepatobiliary centres, we aim to assess the safety/outcomes of hepatic IRE. Materials and Methods Bi-institutional retrospective, longitudinal follow-up series of IRE for primary hepatic malignancy; [hepatocellular carcinoma (n = 20), cholangiocarcinoma (n = 3)] and secondary metastatic disease; colorectal (n = 28), neuroendocrine (n = 1), pancreatic (n = 1), breast (n = 1), gastrointestinal stromal tumour (GIST, n = 1) and malignant thymoma (n = 1). Outcome measures included procedural safety/effectiveness, time to progression and time to death. Results Between 2013 and 2017, 52 patients underwent percutaneous IRE of 59 liver tumours in 53 sessions. All tumours were deemed unsuitable for thermal ablation. Cases were performed using ultrasound (US) or computed tomography (CT) guidance. A complete ablation was achieved in n = 44, (75%) of cases with an overall complication rate of 17% (n = 9). Of the complete ablation group, median time to progression was 8 months. At 12 months, 44% were progression-free (95% CI 30–66%). The data suggest that larger lesion size (> 2 cm) is associated with shorter time to progression and there is highly significant difference with faster time to progression in mCRC compared with HCC. Median survival time was 38 months. Conclusion This bi-institutional review is the largest UK series of IRE and suggests this ablative technology can be a useful tool, but appears to mainly induce local tumour control rather than cure with HCC having better outcomes than mCRC.

Background: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. Methods: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. Results: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). Conclusion: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM., SCOPUS: ar.j, info:eu-repo/semantics/published

Correction to: Nature Metabolism https://doi.org/10.1038/s42255-020-00306-2, published online 9 November 2020. In the version of this article initially published, in the ×40 diseased human kidney images in Supplementary Fig. 1, the FSGS image duplicated the DN image. The error has been corrected in the HTML version of the article.

Background: Irrespective of the underlying aetiology, 90% of hepatocellular carcinomas arise and progress on a background of chronic inflammation. We have explored the independent prognostic value of circulating inflammatory cells. Methods: Peripheral blood count data sets from 583 consecutive patients presenting to a single UK centre (2000–2010) were analysed for associations with tumour stage, liver function, performance status (PST) and survival. Validation was in an independent Hong Kong cohort (585 patients; 2007–2013). Results: In both UK and Hong Kong cohorts, neutrophils, platelets, lymphocytes, the neutrophil/lymphocyte ratio (NLR) and the Systemic Immune-Inflammation Index (SII) correlated stepwise, either increasing or decreasing (lymphocytes), with tumour node metastasis (TNM) and Childs–Pugh stage, PST and consequently with the combined Barcelona Clinic for Liver Cancer stage. Survival analyses confirmed the NLR and SII as highly significant prognostic biomarkers. Focused on individual cell types, only the neutrophil count was independently associated with both TNM stage and PST, as well as being significantly and independently associated with poorer survival. Conclusions: In this study of 1168 patients, neutrophils alone, rather than lymphocytes or platelets, were independently associated with outcome. These data support further characterisation of a potentially distinctive role for neutrophils as facilitators of tumour progression and deteriorating performance.