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2.
Transplantation ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38780399

ABSTRACT

BACKGROUND: The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. METHODS: Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. RESULTS: One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). CONCLUSIONS: A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

3.
Eur J Surg Oncol ; : 108248, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38467524

ABSTRACT

Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.

4.
Transplantation ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38499511

ABSTRACT

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

5.
Am J Transplant ; 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38360185

ABSTRACT

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

7.
Am J Transplant ; 24(1): 104-114, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37666457

ABSTRACT

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.


Subject(s)
Facial Transplantation , Vascularized Composite Allotransplantation , Humans , Facial Transplantation/methods , Consensus , Delphi Technique , Research Design
8.
Transpl Int ; 36: 11673, 2023.
Article in English | MEDLINE | ID: mdl-37727381

ABSTRACT

Universal Hepatitis E Virus (HEV) screening of deceased organ donors was implemented by the UK national organ procurement organisation in October 2017. Donor testing for HEV infection is done post-transplant; detection of HEV ribonucleic acid (RNA) in donor plasma is therefore not a contra-indication for organ donation, with the result being used to inform recipient management. Immediate post-transplant detection of donor HEV viraemia triggers notification to transplant centres. Follow up of liver and kidney recipients has shown that transmission through solid organs is very efficient, particularly through liver grafts, as expected; no other organ types were transplanted in this cohort. Although donors with higher plasma viral load (VL > 103 IU/mL) were invariably associated with recipient infection, transmission was also documented at lower VL levels. Knowledge of donor HEV status has led to identification of transmission of infection via solid organ grafts followed by close patient monitoring and informed clinical management decisions. The purpose of this strategy is to allow early detection of infection and recurrence and treatment to circumvent the risk of accelerated liver damage from chronic HEV infection due to undiagnosed, inadvertent donor-derived transmission of infection.


Subject(s)
Hepatitis E virus , Hepatitis E , Tissue and Organ Procurement , Humans , Tissue Donors , Hepatitis E/diagnosis , United Kingdom
9.
Gut ; 73(1): 16-46, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-37770126

ABSTRACT

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Gastroenterology , Humans , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/therapy , Bile Ducts, Intrahepatic
10.
Cochrane Database Syst Rev ; 8: CD010872, 2023 08 08.
Article in English | MEDLINE | ID: mdl-37551841

ABSTRACT

BACKGROUND: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES: To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA: We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS: We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.


Subject(s)
Fibrin , Hemostatics , Adult , Humans , Blood Loss, Surgical/prevention & control , Fibrin/therapeutic use , Hemostatics/therapeutic use , Liver , Quality of Life
12.
Transplantation ; 107(5): 1124-1135, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36727724

ABSTRACT

BACKGROUND: The effectiveness of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 Omicron variant in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. METHODS: National registries in England were linked to identify SARS-CoV-2 positive tests, noninjury hospitalization within 14 d, and deaths within 28 d between December 7, 2020, and March 31, 2022 in adult SOT recipients. Incidence rate ratios (IRRs) for infection, and hospitalization or death, were adjusted for recipient demographics and calendar month for the Omicron-dominant period (December 20, 2021, to March 31, 2022). Mortality risk following SARS-CoV-2 infection was adjusted for recipient demographics and dominant variant using a Cox proportional-hazards model for the entire time period. RESULTS: During the Omicron-dominant period, infection IRRs (95% confidence intervals) were higher in those receiving 2, 3, and 4 vaccine doses than in unvaccinated patients (1.25 [1.08-1.45], 1.46 [1.28-1.67], and 1.79 [1.54-2.06], respectively). However, hospitalization or death IRRs during this period were lower in those receiving 3 or 4 vaccine doses than in unvaccinated patients (0.62 [0.45-0.86] and 0.39 [0.26-0.58], respectively). Risk-adjusted analyses for deaths after SARS-CoV-2 infection between December 7, 2020, and March 31, 2022, found hazard ratios (95% confidence intervals) of 0.67 (0.46-0.98), 0.46 (0.30-0.69), and 0.18 (0.09-0.35) for those with 2, 3, and 4 vaccine doses, respectively, when compared with the unvaccinated group. CONCLUSIONS: In immunosuppressed SOT recipients, vaccination is associated with incremental, dose-dependent protection against hospitalization or death after SARS-CoV-2 infection, including against the Omicron variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , Vaccine Efficacy , Retrospective Studies , Transplant Recipients , COVID-19/epidemiology , COVID-19/prevention & control , England/epidemiology
13.
Curr Oncol Rep ; 25(2): 135-144, 2023 02.
Article in English | MEDLINE | ID: mdl-36648705

ABSTRACT

PURPOSE OF REVIEW: This review outlines the role of liver transplantation in selected patients with unresectable neuroendocrine tumour liver metastases. It discusses the international consensus on eligibility criteria and outlines the efforts taking place in the UK and Ireland to develop effective national liver transplant programmes for neuroendocrine tumour patients. RECENT FINDINGS: In the early history of liver transplantation, indications included cancer metastases to the liver as well as primaries of liver origin. Often, liver transplantation was a salvage procedure. The early results were disappointing, including in patients with neuroendocrine tumours. These data discouraged the widespread adoption of liver transplantation for neuroendocrine tumour liver metastases (NET LM). A few centres persisted in performing liver transplantation for patients with NET LM and in determining parameters predictive of good outcomes. Their work has provided evidence for benefit of liver transplantation in a selected group of patients with NET LM. Liver transplantation for NET LM is now accepted as a valid indication by many professional bodies, including the European Neuroendocrine Tumour Society (ENETS) and the United Network for Organ Sharing (UNOS). It is nevertheless rarely utilised. The UK and the Republic of Ireland are commencing a pilot programme of liver transplantation in selected patients. This programme will help develop the expertise and infrastructure to make liver transplantation for NET LM a routine procedure.


Subject(s)
Liver Neoplasms , Liver Transplantation , Neuroendocrine Tumors , Humans , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Liver Neoplasms/secondary
14.
Frontline Gastroenterol ; 14(1): 45-51, 2023.
Article in English | MEDLINE | ID: mdl-36561784

ABSTRACT

Objective: Hepatocellular carcinoma (HCC) deaths are rising alarmingly. Many patients are unsuitable for available therapies. Poor response rates further hamper outcomes for those that are. Selective internal radiation therapy (SIRT) offers hope, although which patients benefit over standard approaches remains unclear. Design/method: As a quality/service improvement, we audited consecutive patients treated with SIRT (2015-2020) by the Newcastle upon Tyne Hospitals National Health Service Foundation Trust HCC multidisciplinary team. Indications, Barcelona clinic liver cancer (BCLC) stage, treatment response, subsequent therapies and survival at 30 September 2021 were assessed. Results: Fifty-one patients received SIRT. Thirty-day mortality was zero. Three months partial response, stable disease and progressive disease on imaging were 50%, 22% and 28%, respectively. Overall median survival was 21 months. There were four subgroups: (1) BCLC-B: HCC>7 cm too large for transarterial chemoembolisation (TACE) alone (n=21); (2) BCLC-B: HCC progressed post TACE (n=7); (3) BCLC-C: HCC with any combination of large tumour burden, branch portal vein thrombosis, non-hepatitis C virus aetiology (n=16); (4) BCLC-C: sorafenib inappropriate (n=7). In group 1, 5/21 (23.8%) of patients were downstaged to resection, 33% received subsequent medical therapies and median survival was >40 months. In BCLC-B patients treated second line (group 2), median survival was 14.2 months. In BCLC-C, median survival was 20.2 months for group 3 and 4.2 months for group 4. Conclusion: SIRT outcomes for advanced HCC, often bridging patients with adverse predictive factors to subsequent surgery or medical therapies, were encouraging. A role after TACE or for BCLC-C patients requires further assessment.

15.
Transpl Int ; 36: 11792, 2023.
Article in English | MEDLINE | ID: mdl-38370534

ABSTRACT

90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry (n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30 kg/m2. After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM (n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1 year (p = 0.120), 3 years (p = 0.237), and 10 years (p = 0.196) and kidney GS at 1 year (p = 0.438), 3 years (p = 0.548), and 10 years (p = 0.947). PS was comparable at 1 year (p = 0.886) and 3 years (p = 0.237) and at 10 years (p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS (p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS(p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Pancreas Transplantation , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/surgery , Graft Survival , Kidney , Pancreas , United Kingdom
16.
Eur J Gastroenterol Hepatol ; 34(10): 1060-1066, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36062496

ABSTRACT

INTRODUCTION: Symptomatic umbilical hernias are a common cause of morbidity and mortality in patients with cirrhosis and end-stage liver disease (ESLD). This study set out to characterise the factors predicting outcome following repair of symptomatic umbilical hernias in ESLD at a single institution. METHODS: A retrospective review was performed of all patients with ESLD who underwent repair of a symptomatic umbilical hernia between 1998 and 2020. Overall survival was predicted using the Kaplan-Meier method. Logistic regression was used to determine predictors of decompensation and 30-day, 90-day and 1-year mortality. RESULTS: One-hundred-and-eight patients with ESLD underwent umbilical hernia repair (emergency n = 78, 72.2%). Transjugular shunting was performed in 29 patients (26.9%). Decompensation occurred in 44 patients (40.7%) and was predicted by emergency surgery (OR, 13.29; P = 0.001). Length of stay was shorter in elective patients compared to emergency patients (3-days vs. 7-days; P = 0.003). Thirty-day, 90-day and 1-year survival was 95.2, 93.2 and 85.4%, respectively. Model for ESLD score >15 predicted 90-day mortality (OR, 18.48; P = 0.030) and hyponatraemia predicted 1-year mortality (OR, 5.31; P = 0.047). Transjugular shunting predicted survival at 1 year (OR, 0.15; P = 0.038). CONCLUSIONS: Repair of symptomatic umbilical hernias in patients with ESLD can be undertaken with acceptable outcomes in a specialist centre, however, this remains a high-risk intervention. Patients undergoing emergency repair are more likely to decompensate postoperatively, develop wound-related problems and have a longer length of stay. Transjugular shunting may confer a benefit to survival, but further prospective trials are warranted.


Subject(s)
End Stage Liver Disease , Hernia, Umbilical , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/methods , End Stage Liver Disease/complications , End Stage Liver Disease/diagnosis , End Stage Liver Disease/surgery , Hernia, Umbilical/etiology , Hernia, Umbilical/surgery , Humans , Retrospective Studies , Risk Factors
18.
BMJ Open ; 12(5): e050166, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35551086

ABSTRACT

BACKGROUND: Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS: Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION: The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN14986389.


Subject(s)
Electroporation , Pancreatic Neoplasms , Electroporation/methods , Feasibility Studies , Humans , Multicenter Studies as Topic , Pancreas , Pancreatic Neoplasms/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Pancreatic Neoplasms
19.
Article in English | MEDLINE | ID: mdl-35450934

ABSTRACT

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , COVID-19/epidemiology , Carcinoma, Hepatocellular/epidemiology , Humans , Liver Neoplasms/epidemiology , Pandemics , Retrospective Studies
20.
Article in English | MEDLINE | ID: mdl-35301231

ABSTRACT

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.


Subject(s)
Pancreatic Neoplasms , Endosonography , Humans , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Retrospective Studies , Stents
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