Where Are We Now with Liver Transplantation in Neuroendocrine Neoplasms? The Place of Liver Transplantation for Grades 1 and 2 Well-Differentiated Unresectable Liver Metastatic Neuroendocrine Tumours.

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.

Covered transjugular intrahepatic portosystemic stent-shunt vs large volume paracentesis in patients with cirrhosis: A real-world propensity score-matched study.

BACKGROUND: Refractory ascites has a 1-year survival rate of 50%. In selected patients, treatment options include liver transplantation (LT) or transjugular intrahepatic portosystemic stent shunt (TIPSS). AIM: To assess the outcomes of patients who underwent a TIPSS compared to large volume paracentesis (LVP). METHODS: Retrospective study of patients who underwent a covered TIPSS or LVP for refractory or recurrent ascites over 7 years. Primary outcome was transplant-free survival (TFS). Further analysis was done with propensity score matching (PSM). RESULTS: There were 150 patients [TIPSS group (n = 75), LVP group (n = 75)]. Seven patients in the TIPSS group underwent LT vs 22 patients in the LVP group. Overall median follow up, 20 (0.47-179.53) mo. In the whole cohort, there was no difference in TFS [hazard ratio (HR): 0.80, 95% confidence interval (CI): 0.54-1.21]; but lower de novo hepatic encephalopathy with LVP (HR: 95%CI: 0.20-0.96). These findings were confirmed following PSM analysis. On multivariate analysis albumin and hepatocellular carcinoma at baseline were associated with TFS. CONCLUSION: Covered TIPSS results in similar TFS compared to LVP in cirrhotic patients with advanced liver failure. Liver transplant assessment should be considered in all potential candidates for TIPSS. Further controlled studies are recommended to select appropriate patients for TIPSS.

Management of Ascites Following Deceased Donor Liver Transplantation: A Case Series.

Background: Persistent ascites after orthotropic liver transplantation has numerous causes and can be challenging to manage. This study aimed to determine the outcomes associated with conservative and endovascular intervention of posttransplant ascites after deceased donor liver transplantation. Methods: Adult (≥18 y) liver transplant recipients (between 2006 and 2019) who underwent hepatic venous pressure studies to investigate posttransplant ascites were included in this retrospective study. Comparisons were made between those who were managed with conservative therapy versus endovascular intervention and were also based on hepatic venous wedge pressure gradient (normal [≤10 mm Hg] versus elevated [>10 mm Hg]). Results: A total of 30 patients underwent hepatic venography to investigate ascites during the study period. The median time from transplant to venography was 70 d. At least 1 endovascular intervention was performed in 18 of 30 patients (62%), and 12 of 30 patients (38%) were managed conservatively. Endovascular interventions included angioplasty (n = 4), hepatic vein stenting (n = 9), or a transjugular intrahepatic portosystemic shunt (n = 7). The mean (range) hepatic venous wedge pressure gradient for the conservative and endovascular intervention groups was 12 mm Hg (3-23) and14 mm Hg (2-35), respectively. At a 6-mo follow-up, ascites resolved in 6 of 12 patients (50%) and 11 of 18 patients (61%) in the medical management and endovascular groups, respectively. The graft survival rates at 6 and 12 mo were (7/12 [58%] versus 17/18 [94%], P = 0.02) and (7/12 [58%] versus 14/18 [78%], P = 0.25), respectively. Conclusions: Despite medical or endovascular intervention, resolution of ascites is achieved in <60% of patients with persistent ascites. Biopsy findings and venographic pressure studies should be carefully integrated into the management of posttransplant ascites.

The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study.

Prothrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model.

Tunnelled peritoneal drainage catheter placement for the palliative management of refractory ascites in patients with liver cirrhosis.

OBJECTIVE: Refractory ascites is an established indication for liver transplantation. While transplantation is regarded as the definitive therapy for this condition, many patients are unsuitable due to comorbidity or frailty. Alternatives such as transjugular intrahepatic portosystemic shunt (TIPSS) and large-volume paracentesis can lead to complications, including encephalopathy, circulatory and renal dysfunction, and protein-calorie deficiency that may accelerate sarcopenia. Cost and complication rates limit therapies such as alfapump. While there are data to support the use of indwelling catheters in the management of patients with malignant ascites, there is limited evidence to support their routine use in the context of end-stage liver cirrhosis. Here we describe our centres' experience using indwelling tunnelled ascitic drains over a 6-year period. METHODS: A retrospective review of data (January 2012-May 2018) was undertaken for all patients with refractory ascites who underwent a tunnelled ascitic drain. Demographics, disease aetiology, procedure data and follow-up data were obtained through interrogation of electronic records and reports. RESULTS: Twenty-five drains were placed. All procedures were technically successful with no immediate complications. Six patients were readmitted following their index admission with abdominal pain and suspected infected ascites (although only two had a positive ascitic fluid culture). There were three cases of abdominal wall cellulitis and three of leakage around the tunnel site; all managed conservatively. CONCLUSION: Indwelling drains appear an effective strategy for palliative management of select patients with liver cirrhosis complicated by refractory ascites who are not amenable to undergo TIPSS or transplantation. While complications can occur, these are most usually minor and can be managed on an outpatient basis.

Portal decompression with transjugular intrahepatic portosystemic shunt prior to nonhepatic surgery: a single-center case series.

BACKGROUND AND AIMS: Cirrhosis increases perioperative and postoperative mortality in nonhepatic surgery. Transjugular intrahepatic portosystemic shunt (TIPSS), by reducing portal pressure, may reduce intraoperative bleeding and postoperative decompensation. We report our experience of prophylactic TIPSS in nonhepatic surgery. METHODS: Patients who underwent prophylactic TIPSS before nonhepatic surgery were identified from database with retrospective data collection via an e-patient record system. Primary outcome was discharged without hepatic decompensation after a planned surgery. RESULTS: Twenty-one patients [age (median, range): 55, 33-76 years, Child's score: 6, 5-9] who underwent prophylactic TIPSS before nonhepatic surgery over a period of 9 years were included. All patients underwent successful TIPSS with a reduction in portal pressure gradient from 21.5 (11-35) to 16 (7-25) mmHg (P < 0.001). Immediate post-TIPSS complications were seen in 7 (33%) patients including hepatic encephalopathy in four. Eighteen patients (86%) underwent planned surgical intervention. Significant postoperative complications included hepatic encephalopathy (3), sepsis (2) and bleed (1). Two patients died postoperatively with multi-organ failure. The primary outcome was achieved in 12 (57%) patients. Post-TIPSS portal pressure gradient was significantly higher in patients with the adverse primary outcome. Over a follow-up period of 11 (1-78) months; 1-, 6- and 12-months' survival was 90, 80 and 76%, respectively. CONCLUSION: Prophylactic TIPSS is associated with complications in up to one-third of patients, with 57% achieving the primary outcome. Careful patient selection in a multidisciplinary team setting is essential. Multicentre studies are necessary before the universal recommendation of prophylactic TIPSS.

An Extension of the Bollinger Scoring System to Analyse the Distribution of Macrovascular Disease of the Lower Limb in Diabetes.

OBJECTIVE: While it is generally considered that patients with diabetes mellitus (DM) have more distal peripheral arterial disease (PAD), there is little information on how individual vessels are affected. The aim of this study was to adapt Bollinger's scoring system for lower limb angiograms (DSAs) to include the distal and planter vessels. The reliability of this extension was tested and was used to compare the distribution of disease in two cohorts of patients with and without DM. METHODS: Patients who had undergone DSA ± angioplasty for PAD at a single centre between September 2010 and April 2014 were identified. Twenty-five patients' images were reviewed by four clinicians and scored using an extended version of the Bollinger score. A total of 153 patients with DM were matched, for age, sex, ethnicity, smoking, and hypertension, with 153 patients without DM. The infrainguinal vessels were divided into 16 arterial segments, including plantar vessels, and scored using the Bollinger score. The score ranges from 0 to 15. Fifteen represents an arterial segment with more than 50% of its length occluded. Interobserver reliability was tested using interclass correlation (ICC) and Cohen's kappa coefficient. RESULTS: The ICC demonstrated good agreement between observers (0.76 [0.72-0.79]) with good internal consistency (Cronbach's alpha 0.93). When the Bollinger scores were categorised, the results were weaker, Cohen's kappa ranged from 0.39 (standard error 0.033) to 0.54 (0.030). Patients with DM had a higher burden of disease in the anterior tibial and posterior tibial arteries with relative sparing of the peroneal artery and no difference in the plantar vessels. CONCLUSION: It has been demonstrated that the Bollinger score can be extended to include the distal vessels. This amended scoring system can be used to compare the burden of distal disease in patients with PAD. How the score relates to clinical presentation and outcomes needs further investigation.

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology.

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report.

Translumbar Embolization of Type II Endoleaks: 12 Years of Experience at a Regional Vascular Centre.

BACKGROUND AND AIMS: The management of persistent type II endoleaks (T2E) is often problematic for the endovascular specialist, with a lack of clear evidence for the best approach for embolization. The aim of this study was to evaluate the safety and efficacy of translumbar embolization (TLE) for T2E following endovascular aneurysm repair (EVAR). METHODS: This retrospective review included 27 embolizations performed on 23 patients with a median age of 78 (range 67-94 years; male: female 15:9), during the period September 2006 to July 2018. Primary outcome was freedom from aneurysm sac growth defined as <2 mm sac diameter increase on subsequent computed tomography. RESULTS: The initial technical success rate was 100%, with complete "on table" embolization of the T2E on fluoroscopy; however, 4 (15%) patients needed repeat TLE due to persistent endoleak identified on follow-up computed tomography or because of further sac expansion. Satisfactory stasis was achieved in these 4 cases following a second embolization. The mean volume of embolic injected was 7.4 mL per case. Feeding vessels were identified on angiography in all cases; the nidus was supplied by lumbar branches in 21 cases, by the inferior mesenteric artery in 1 case and by both in a further 5 cases. Freedom from aneurysm sac growth (defined as < 2 mm) following 1 or 2 separate TLE was achieved in 18 (78%) and 20 (86%) patients, respectively. The major complication rate was <5% with one case of psoas abscess presenting 7 months following embolization; there were 2 minor complications in the form of intraprocedural transient abdominal pain. CONCLUSION: The translumbar approach is a safe and effective technique to treat T2E, as evidenced by the low complication and reintervention rate.

Operative management of tennis elbow: a quantitative review.

INTRODUCTION: The results of operative management of tennis elbow are varied, and the indications for surgery are not well codified. Many operative techniques are reported, but a clear consensus on whether a given surgical procedure is more effective over another is yet to be reached. METHODS: We conducted a MEDLINE, CINAHL and EMBASE search on all available scientific articles that reported the outcomes of surgery for lateral epicondylopathy. Keywords used were 'tennis elbow', 'lateral epicondylitis', 'lateral epicondylalgia', 'tendinopathy', 'tendonitis' and 'tendon'. Subheadings used were 'surgery', 'outcomes', 'pathology', 'physiology' and 'operation'. All relevant articles were retrieved. Each article was scored using the Coleman methodology score (CMS), a highly repeatable methodology score, by two independent reviewers, followed by data analysis. RESULTS: The mean CMS for the 45 studies identified was 43 +/- 9 (of a possible 100 points), with 'number of patients', 'type of study', 'outcome criteria and assessment' and 'subject selection process' being the major low scorers. Also, there was no improvement in the CMS, and hence study design, over the years (intra-class correlation coefficient = 0.45). DISCUSSION: There is a dearth of quality evidence available to be able to advocate one operative technique over another. CONCLUSION: We stress the need for well-designed adequately powered randomized controlled trials to be able to understand which of these operative techniques is really superior to the others.