Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease.

BACKGROUND: Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M-PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy. METHODS: Retrospective analysis of outcomes data of UM patients receiving M-PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively. RESULTS: A total of 51 patients received 134 M-PHP procedures (median of 2 M-PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow-up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non-hematologic grade 3-4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9). CONCLUSIONS: M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

Quality of life after melphalan percutaneous hepatic perfusion for patients with metastatic uveal melanoma.

BACKGROUND: Recent studies indicate that melphalan percutaneous hepatic perfusion (M-PHP) for liver metastases from ocular melanoma (mUM) improves survival. Importantly, this benefit must be carefully balanced with changes in a patient's quality of life (QoL). This study examines the QoL changes post-M-PHP. METHODS: Retrospective analysis of the change in QoL using the Functional Assessment of Cancer Therapy-General (FACT-G) with mUM patients receiving M-PHP ( n  = 20). The FACT-G scores, which comprise physical (PWB), social (SWB), emotional (EWB) and functional (FWB) wellbeing were measured pre-procedure and at day 1, day of discharge (mean = 2.4 days), 7, 14 and 28 days after M-PHP therapy. Wilcoxon signed-rank test gauged QoL domain changes. RESULTS: Baseline FACT-G median (IQR) scores were 101.8 (21.8). QoL scoring significantly decreased immediately after the procedure [day 1; 85 (27.5); P  = 0.002] and gradually improved over time. By day 28, QoL almost returned to pre-procedure levels [100.3 (13.8); P  = 0.31]. Subscore analysis revealed that the initial drop in QoL at day 1 post-procedure was attributable to the PWB (28 vs. 24; P  = 0.001) and FWB domains (26 vs. 18.5; P  < 0.001). By day 28 there was a statistically significant improvement in EWB ( P  = 0.01). CONCLUSION: QoL following M-PHP decreases immediately after therapy and is not significantly different from baseline by the day of discharge. By day 28 there is improved emotional well-being. This study could help to optimize the time between treatment cycles when combined with toxicity data and blood count recovery.

Liver resection for metastatic uveal melanoma: experience from a supra-regional centre and review of literature.

Management of liver metastases from uveal melanoma (LMUM) requires multimodal approach. This study describes evolution of liver resection for LMUM, reviewing current literature and institutional outcomes. Records of patients referred to the Melanoma Multi-Disciplinary Team between February 2005 and August 2018 were reviewed. All publications describing surgery for LMUM were identified from PubMed, Embase, and Google Scholar. Thirty-one of 147 patients with LMUM underwent laparoscopic liver biopsy, and 29 (14 females) had liver resections. Nineteen liver resections were performed locally [7 major (≥3 seg), 14 laparoscopic] without major complications or mortality. Overall survival positively correlated with the time from uveal melanoma to LMUM (Spearman's rho rs = 0.859, P < 0.0001). Overall and recurrence-free survivals were comparable following R1 or R0 resections (OS 25 vs. 28 months, P = 0.404; RFS 13 vs. 6 months, P = 0.596). R1 resection cohort had longer lead-time (median 100 vs. 24 months, P = 0.0408). Eleven publications describing liver resection for LMUM were identified and included in the narrative review. Surgery for LMUM is safe and complements multidisciplinary management. Despite heterogeneity in literature, time from diagnosis of uveal melanoma to LMUM remains a key factor affecting survival after liver resection.

Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma.

Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10-25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016-2020 vs. 2012-2016 (0.17 vs. 0.90 per patient, P < 0.001). M-PHP provides excellent response rates and PFS compared with other available treatments, with decreasing side effect profile with experience. Combination therapy with systemic agents may be viable to further advance OS.

Attitudes to radiation safety and cholangiogram interpretation in endoscopic retrograde cholangiopancreatography (ERCP): a UK survey.

BACKGROUND: Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) exposes staff and patients to potentially harmful ionizing radiation. We performed a UK survey to explore trainee and trainer attitudes to radiation protection and cholangiogram interpretation in ERCP. METHODS: An electronic 10-point survey was prospectively distributed to endoscopy unit leads, training programme directors between October and November 2019. Only UK-based ERCP trainees and trainers with hands-on procedural exposure were eligible for the survey. RESULTS: The survey was completed by 107 respondents (58 trainees and 49 trainers), with an estimated overall response rate of 46%. Overall, 49% of respondents were up to date with their radiation protection course, 38% were aware of European Basic safety standards directive (BSSD), 38% wore radiation protection goggles, and 40% were aware of the average radiation screening dose per ERCP procedure. Compared with trainers, trainees were less likely to routinely wear thyroid protection shields (76% vs 92%; p=0.028), have awareness of the BSSD (20% vs 49%; p=0.037) or know their average procedural radiation dosages (21% vs 63%; p<0.001). With regard to cholangiogram interpretation, only 26% had received formal training, with 97% of trainees expressing a desire for further training. CONCLUSION: This survey highlights a relative complacency in safety attitudes to radiation protection during ERCP. These data provide impetus to improve training and quality assurance in radiation protection, which should be regarded as a mandatory safety aspect prior to commencing hands-on ERCP training.

Feasibility of laparoscopic distal spleno-pancreatectomy following previous necrosectomy. A case report.

CONTEXT: In recent years, laparoscopic approach to distal pancreatectomy has been increasingly favoured following several reports showing reductions in morbidity and hospital stay compared with open surgery. Previous major abdominal surgery is a relative contraindication for most laparoscopic procedures including distal pancreatectomy. CASE REPORT: We present a case of a young woman in whom we attempted and accomplished safely, a laparoscopic distal pancreatectomy despite having had major pancreatic necrosectomy and discuss the feasibility of this approach. CONCLUSION: It is possible to perform complex laparoscopic pancreatic resections safely in centres with special interest and expertise.

Describing Peripancreatic Collections According to the Revised Atlanta Classification of Acute Pancreatitis: An International Interobserver Agreement Study.

OBJECTIVES: Severe acute pancreatitis is associated with peripancreatic morphologic changes as seen on imaging. Uniform communication regarding these morphologic findings is crucial for accurate diagnosis and treatment. For the original 1992 Atlanta classification, interobserver agreement is poor. We hypothesized that for the revised Atlanta classification, interobserver agreement will be better. METHODS: An international, interobserver agreement study was performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15), and gastroenterologists (n = 8). Representative computed tomographies of all stages of acute pancreatitis were selected from 55 patients and were assessed according to the revised Atlanta classification. The interobserver agreement was calculated among all reviewers and subgroups, that is, expert and nonexpert reviewers; interobserver agreement was defined as poor (≤0.20), fair (0.21-0.40), moderate (0.41-0.60), good (0.61-0.80), or very good (0.81-1.00). RESULTS: Interobserver agreement among all reviewers was good (0.75 [standard deviation, 0.21]) for describing the type of acute pancreatitis and good (0.62 [standard deviation, 0.19]) for the type of peripancreatic collection. Expert radiologists showed the best and nonexpert clinicians the lowest interobserver agreement. CONCLUSIONS: Interobserver agreement was good for the revised Atlanta classification, supporting the importance for widespread adaption of this revised classification for clinical and research communications.

Laparoscopic liver resection for lesions adjacent to major vasculature: feasibility, safety and oncological efficiency.

BACKGROUND AND OBJECTIVES: Laparoscopic liver resection for lesions adjacent to major vasculature can be challenging, and many would consider it a contraindication. Recently, however, laparoscopic liver surgeons have been pushing boundaries and approached some of these lesions laparoscopically. We assessed feasibility, safety and oncological efficiency of this laparoscopic approach for these lesions. METHODS: This is a monocenter study (2003-2013) describing technique and outcomes of laparoscopic liver resection for lesions adjacent to major vasculature: <2 cm from the portal vein (main trunk and first division), hepatic arteries or inferior vena cava. RESULTS: Thirty-seven patients underwent laparoscopic liver resection (LLR) for a lesion adjacent to major vasculature. Twenty-four (65%) resections were for malignant disease and 92% R0 resections. Conversion occurred in three patients (8%). Mean operative time was 313 min (standard deviation (SD) ± 101) and intraoperative blood loss 400 ml (IQR 213-700). Clavien-Dindo complications > II occurred in two cases (5%), with no mortality. Lesions at <1 cm were larger (7.2 cm (2.7-14) vs. 3 cm (2.5-5), p = 0.03) and operation time was longer (344 ± 94 vs. 262 ± 92 min, p = 0.01) than lesions at 1-2 cm from major vasculature. CONCLUSIONS: Lesions <2 cm from major hepatic vasculature do not represent an absolute contraindication for LLR when performed by experienced laparoscopic liver surgeons in selected patients.

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a 'real-world' UK health economic evaluation.

OBJECTIVE: To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. DESIGN: A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. SETTING: Secondary care. PATIENTS: Cirrhotic patients with refractory ascites. MAIN OUTCOME MEASURES: We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. RESULTS: Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. CONCLUSIONS: TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.

Vascular supply to the liver: a report of a rare arterial variant.

In the classic description of hepatic arterial supply, the common hepatic artery originates from the coeliac trunk. However, there are numerous variations to this classic pattern. We report a rare variant pattern of hepatic arterial supply and discuss the clinical significance of this variation.

Management of median arcuate ligament syndrome in patients who require pancreaticoduodenectomy.

Pancreaticoduodenectomy is the standard treatment for localised neoplasms of the pancreatic head. The operation can be performed safely in specialist units but good outcome is compromised if postoperative blood flow to the liver and biliary tree is inadequate. Coeliac artery occlusion with blood supply to the liver arising from the superior mesenteric artery via the gastroduodenal artery is difficult to recognise, especially intraoperatively. Recognition of absent hepatic artery pulsation after occlusion of the gastroduodenal artery opens a dilemma: should the resection be abandoned or should vascular reconstruction be undertaken, adding risk to an already complex procedure? We describe two cases with a resectable pancreatic endocrine tumour in which coeliac artery occlusion caused by median arcuate ligament compression was identified from cross-sectional imaging and reconstructions. We highlight two different strategies to correct the vascular insufficiency and allow safe pancreatic resection.

Arterialised hepatic nodules in the Fontan circulation: hepatico-cardiac interactions.

Hypervascular nodules occur commonly when there is hepatic venous outlet obstruction. Their nature and determinants in the Fontan circulation is poorly understood. We reviewed the records of 27 consecutive Fontan patients who had computerized tomography scan (CT) over a 4 year period for arterialised nodules and alterations in hepatic flow patterns during contrast enhanced CT scans and related these findings to cardiac characteristics. Mean patient age was 24 ± 5.8 years, (range 16.7-39.8) and mean Fontan duration was 16.8 ± 4.8 years (range 7.3-28.7). Twenty-two patients demonstrated a reticular pattern of enhancement, 4 a zonal pattern and only 1 demonstrated normal enhancement pattern. Seven (26%) patients had a median of 4 (range 1-22) arterialised nodules, mean size 1.8 cm (range 0.5 to 3.2 cm). All nodules were located in the liver periphery, their outer aspect lying within 2 cm of the liver margin. Patients with nodules had higher mean RA pressures (18 mmHg ± 5.6 vs. 13 mmHg ± 4, p=0.025), whereas their mixed venous saturation and aortic saturation was not significantly different (70% ± 11 vs. 67% ± 9 and 92% ± 10 vs. 94% ± 4, p>0.05). Post-mortem histology suggests focal nodular hyperplasia is the underlying pathology. ConclusionsAbnormalities of hepatic blood flow and the presence of arterialised nodules are common in the failing Fontan circulation. They occur especially when central venous pressures are high, and very likely indicate arterialisation of hepatic blood flow and reciprocal portal venous deprivation. The underlying pathology is most likely focal nodular hyperplasia.

Management of renal tumors by image-guided radiofrequency ablation: experience in 105 tumors.

AIMS: In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. MATERIALS AND METHODS: RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. RESULTS: Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson chi(2)) Five patients had complications. There have been no local recurrences. CONCLUSION: Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors.

Hepatic changes in the failing Fontan circulation.

BACKGROUND: The failing Fontan circulation is associated with hepatic impairment. The nature of this liver injury is poorly defined. OBJECTIVE: To establish the gross and histological liver changes of patients with Fontan circulation relative to clinical, biochemical and haemodynamic findings. METHODS: Patients were retrospectively assessed for extracardiac Fontan conversion between September 2003 and June 2005, according to an established clinical protocol. Twelve patients, mean age 24.6 (range 15.8-43.4) years were identified. The mean duration since the initial Fontan procedure was 14.1 (range 6.9-26.4) years. RESULTS: Zonal enhancement of the liver (4/12) on CT was more common in patients with lower hepatic vein pressures (p = 0.007), and in those with absent cardiac cirrhosis on histological examination (p = 0.033). Gastro-oesophageal varices (4/12) were more common in patients with higher hepatic vein pressure (21 (6.3) vs 12.2 (2.2) mm Hg, p = 0.013) and associated with more advanced cirrhosis (p = 0.037). The extent of cirrhosis (7/12) was positively correlated with the hepatic vein pressure (r = 0.83, p = 0.003). A significant positive correlation was found between the Fontan duration and the degree of hepatic fibrosis (r = 0.75, p = 0.013), as well as presence of broad scars (r = 0.71, p = 0.021). Protein-losing enteropathy (5/12) occurred more frequently in patients with longer Fontan duration (11.7 (3.2) vs 17.9 (6.1) years, p = 0.038). CONCLUSIONS: Liver injury, which can be extensive in this patient group, is related to Fontan duration and hepatic vein pressures. CT scan assists non-invasive assessment. Cardiac cirrhosis with the risk of developing gastro-oesophageal varices and regenerative liver nodules, a precursor to hepatocellular carcinoma, is common in this patient group.

Intrahepatic arterioportal shunting and anomalous venous drainage: understanding the CT features in the liver.

The increased use of high-contrast volume, arterial-phase studies of the liver has demonstrated the frequent occurrence of arterioportal shunts within both the cirrhotic and non-cirrhotic liver. This article sets out to explain the underlying microcirculatory mechanisms behind these commonly encountered altered perfusion states. Similarly, well-recognised portal perfusion defects occur around the perifalciform and perihilar liver and are largely caused by anomalous venous drainage via the paraumbilical and parabiliary venous systems. The underlying anatomy will be discussed and illustrated. These vascular anomalies are all caused by or result in diminished portal perfusion and are often manifest in the setting of portal venous thrombosis. The evolving concept of zonal re-perfusion following portal vein thrombosis will be discussed.