Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic.

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien-Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting.

Donor-Recipient Body Surface Area Mismatch and the Outcome of Liver Transplantation in the UK.

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area ratio or body surface area index with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low body surface area index cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the body surface area index and compared to complications, graft and recipient survival. Results: The body surface area index ranged from 0.491 to 1.691 with a median of 0.988. The body surface area index > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with body surface area index ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or body surface area index > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P < 0.001) than those with intermediate values. The graft survival rates were reduced by 2% for cases with body surface area index ≤ 0.85 but were decreased by 20% for cases with body surface area index > 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants.

In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery, or portal vein thrombosis? A systematic review of the literature and expert panel recommendations.

BACKGROUND: A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding (CRD42021244288). RESULTS: Of the 2478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS: Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT.

Combining Donor and Recipient Age With Preoperative MELD and UKELD Scores for Predicting Survival After Liver Transplantation.

OBJECTIVES: The end-stage liver disease scoring systems MELD, UKELD, and D-MELD (donor age × MELD) have had mediocre results for survival assessment after orthotopic liver transplant. Here, we introduced new indices based on preoperative MELD and UKELDscores and assessed their predictive ability on survival posttransplant. MATERIALS AND METHODS: We included 1017 deceased donor orthotopic liver transplants that were performed between 2008 (the year UKELD was introduced) and 2019. Donor and recipient characteristics, liver disease scores, transplant characteristics, and outcomes were collected for analyses. D-MELD, D-UKELD (donor age × UKELD),DR-MELD[(donor age + recipient age) × MELD], and DR-UKELD [(donor age + recipient age) × UKELD] were calculated. RESULTS: No score had predictive value for graft survival. For patient survival,DR-MELD and DR-UKELD provided the best results but with low accuracy. The highest accuracy was observed at 1 year posttransplant (areas under the curve of 0.598 [95% CI, 0.529-0.667] and 0.609 [95% CI, 0.549-0.67]forDR-MELDandDR-UKELD). Addition of donor and recipient age significantly improved the predictive abilities of MELD and UKELD for patient survival, but addition of donor age alone did not. For 1-year mortality (using receiver operating characteristic curves), optimal cut-off points were DR-MELD>2345 and DR-UKELD>5908. Recipients with DR-MELD >2345 (P < .001) and DR-UKELD >5908 (P = .002) had worse patient survival within the first year, but only DR-MELD >2345 remained significant after multivariable analysis (P = .007). CONCLUSIONS: DR-MELD and DR-UKELD scores provided the best, albeit mediocre, predictive ability among the 6 tested models, especially at 1 year after posttransplant, although only for patient but not for graft survival. A DR-MELD >2345 was considered to be an additional independent risk factor for worse recipient survival within the first postoperative year.

Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology.

Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage normothermic machine perfusion (pSCS-NMP) in liver transplantation. In this multicenter prospective study, 31 livers were transplanted. The primary endpoint was 30-day graft survival. Secondary endpoints included the following: peak posttransplant aspartate aminotransferase (AST), early allograft dysfunction (EAD), postreperfusion syndrome (PRS), adverse events, critical care and hospital stay, biliary complications, and 12-month graft survival. The 30-day graft survival rate was 94%. Livers were preserved for a total of 14 hours 10 minutes ± 4 hours 46 minutes, which included 6 hours 1 minute ± 1 hour 19 minutes of static cold storage before 8 hours 24 minutes ± 4 hours 4 minutes of NMP. Median peak serum AST in the first 7 days postoperatively was 457 U/L (92-8669 U/L), and 4 (13%) patients developed EAD. PRS was observed in 3 (10%) livers. The median duration of initial critical care stay was 3 days (1-20 days), and median hospital stay was 13 days (7-31 days). There were 7 (23%) patients who developed complications of grade 3b severity or above, and 2 (6%) patients developed biliary complications: 1 bile leak and 1 anastomotic stricture with no cases of ischemic cholangiopathy. The 12-month overall graft survival rate (including death with a functioning graft) was 84%. In conclusion, this study demonstrates that pSCS-NMP was feasible and safe, which may facilitate clinical adoption.

Quality assessment of patient information on the management of gallstone disease in the internet - A systematic analysis using the modified ensuring quality information for patients tool.

INTRODUCTION: The internet has become a fundamental source of medical information for patients, however, little is known about the quality of patient information regarding the management of gallstone disease (GD). METHODS: A systematic review of information on GD in the internet was performed. The top 100 websites for every different search term and search engine were assessed using the validated EQIP tool (Score 0-36). RESULTS: A total of 2000 websites were identified and 212 (11%) were eligible for analysis. The overall median EQIP score of all websites was 15 (IQR 13-18). Of all websites, 63% originated from North America however, these represented the lowest median EQIP score of 15. Only 41% of the websites differentiated between clinical presentations and 19% provided emergency information. Only 3% of the websites reported complication rates, ranging from 3 to 36%. CONCLUSION: This is a comprehensive assessment of online patient information on GD using the EQIP tool. The assessment of the quality of websites concerning GD by the EQIP tool indicates that the majority of sites were of low-quality information. There is an immediate need for better informative and educational websites regarding GD that are compatible with international quality standards.

Piggyback or Cava Replacement: Which Implantation Technique Protects Liver Recipients From Acute Kidney Injury and Complications?

The cava-preserving piggyback (PB) technique requires only partial cava clamping during the anhepatic phase in liver transplantation (LT) and, therefore, maintains venous return and may hemodynamically stabilize the recipient. Hence, it is an ongoing debate whether PB implantation is more protective from acute kidney injury (AKI) after LT when compared with a classic cava replacement (CR) technique. The aim of this study was to assess the rate of AKI and other complications after LT comparing both transplant techniques without the use of venovenous bypass. We retrospectively analyzed the adult donation after brain death LT cohort between 2008 and 2016 at our center. Liver and kidney function and general outcomes including complications were assessed. Overall 378 transplantations were analyzed, of which 177 (46.8%) were performed as PB and 201 (53.2%) as CR technique. AKI occurred equally often in both groups. Transient renal replacement therapy was required in 22.6% and 22.4% comparing the PB and CR techniques (P = 0.81). Further outcome parameters including the complication rate were similar in both cohorts. Five-year graft and patient survival were comparable between the groups with 81% and 85%, respectively (P = 0.48; P = 0.58). In conclusion, both liver implantation techniques are equal in terms of kidney function and overall complications following LT.

A randomized trial of normothermic preservation in liver transplantation.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

Portal vein pseudoaneurysm secondary to pancreatic lymphoma and biliary stent insertion: a rare cause of haemobilia.

BACKGROUND: Haemobilia, defined as bleeding from the biliary tree, is a rare entity. The most common cause of haemobilia is iatrogenic trauma, which accounts for 70% of cases. Pseudoaneurysms of the portal vein are an extremely rare cause of haemobilia with only four reported cases to date. Conservative treatment, open surgical repair and percutaneous trans hepatic stent-grafting have all been employed in these cases. This displays the lack of consensus regarding the treatment of this condition.We report the first case of a portal vein pseudoaneurysm following endoscopic common bile duct stent placement performed to relieve obstruction of the common bile duct for lymphomatous infiltration of the pancreatic head. The pseudoaneurysm was successfully treated by placement of a percutaneous trans hepatic covered stent-graft. CASE PRESENTATION: A 42-year-old man with a history of lymphomatous infiltration of the pancreatic head and recent endoscopic common bile duct stent placement presented with sudden onset large volume haematemesis. On the portal venous phase of a triple phase CT, this was found to be secondary to a portal vein pseudoaneurysm bulging into the upper portion of the indwelling biliary stent. The pseudoaneurysm was successfully treated by percutaneous trans hepatic placement of a covered vascular stent-graft. CONCLUSIONS: We report a rare case of portal vein pseudo aneurysm successfully treated by percutaneous trans hepatic portal venous covered vascular stent-graft insertion.

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study.

BACKGROUND: Ischaemia Reperfusion (IR) injury is a major cause of morbidity, mortality and graft loss following Orthotopic Liver Transplantation (OLT). Utilising marginal grafts, which are more susceptible to IR injury, makes this a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in experimental models. Whether RIPC can reduce IR injury in human liver transplant recipients is unknown. METHODS: Forty patients undergoing liver transplantation were randomized to RIPC or a sham. RIPC was induced through three 5 min cycles of alternate ischaemia and reperfusion of the left leg prior to surgery. Data on clinical outcomes was collected prospectively. Per-operative cytokine levels were measured. RESULTS: Fourty five of 51 patients approached (88%) were willing to enroll in the study. Five patients were excluded and 40 randomized, of which 20 underwent RIPC which was successfully completed in all patients. There were no complications following RIPC. Median day 3 AST levels were slightly higher in the RIPC group (221 IU vs 149 IU, p = 1.00). CONCLUSIONS: RIPC is acceptable and safe in liver transplant recipients. This study has not demonstrated evidence of a reduction in short-term measures of IR injury. Longer follow up will be required and consideration of an altered protocol.

Surgical issues in retrieval and implantation.

With increasing demand for organ transplantation and patients deteriorating or dying on the waiting list, organs are now being increasingly used from donors previously considered too marginal. This requires improvements to donor management during the retrieval process, and of the organ during transport and subsequent implantation, in order to maintain outcomes.

Radiological tumor density and lymph node size correlate with survival in resectable adenocarcinoma of the pancreatic head: A retrospective cohort study.

INTRODUCTION: Tumors within the pancreatic head show a variable density and enhancement on computerized tomography (CT). The relationship between the radiological appearance of pancreatic adenocarcinoma on CT and survival remains unclear. The aim of this study was to evaluate the relationship between the tumor density on CT and survival. We also evaluated the correlation between lymph node (LN) size and overall survival in patients undergoing pancreaticoduodenectomy for head of pancreas adenocarcinoma. MATERIALS AND METHODS: Case records of patients undergoing pancreaticoduodenectomy for the adenocarcinoma of pancreas head, between 2005 and 2009, were evaluated. CT was interpreted to document tumor density - Hounsfield unit (HU) and LN size of enlarged LNs. Histology was analyzed to review tumor differentiation and LN status. Survival was correlated with LN size and tumor density (HU). RESULTS: Increasing tumor density was significantly associated with an adverse outcome (P = 0.042, hazard ratio [HR] 1.034, 1.002-1.067 95% confidence interval [95% CI]). Patients with well-differentiated tumors had significantly lower tumor density as compared to moderately differentiated tumors (39.00 ± 26.00 vs. 71.31 ± 21.03 HU, P = 0.005). LN size more than 1 cm irrespective of LN status strongly correlated with the survival and was found to be an important prognostic factor (19.37 ± 2.71 months vs. 27.44 ± 2.74 months; P = 0.025; HR 2.70; 1.09-6.68 95% CI). CONCLUSION: Increasing pancreatic tumor density and the lymph nodal size of more than 1 cm are strong predictors of unfavorable overall survival for resectable adenocarcinoma of the pancreatic head. Further studies are required to identify the value of these proposed prognostic factors.

Demonstration of Calreticulin Expression in Hamster Pancreatic Adenocarcinoma with the Use of Fluorescent Gold Quantum Dots.

BACKGROUND: There is dire need for discovery of novel pancreatic cancer biomarkers and of agents with the potential for simultaneous diagnostic and therapeutic capacity. This study demonstrates calreticulin expression on hamster pancreatic adenocarcinoma via bio-conjugated gold quantum dots (AuQDs). MATERIALS AND METHODS: Hamster pancreatic adenocarcinoma cells were cultured, fixed and incubated with fluorescent AuQDs, bio-conjugated to anti-calreticulin antibodies. Anti-calreticulin and AuQDs were produced in-house. AuQDs were manufactured to emit in the near-infrared. Cells were further characterized under confocal fluorescence. RESULTS: AuQDs were confirmed to emit in the near-infrared. AuQD bio-conjugation to calreticulin was confirmed via dot-blotting. Upon laser excitation and post-incubation with bio-conjugated AuQDs, pancreatic cancer cell lines emitted fluorescence in near-infrared. CONCLUSION: Hamster pancreatic cancer cells express calreticulin, which may be labelled with AuQDs. This study demonstrates the application of nanoparticle-based theranostics in pancreatic cancer. Such biomarker-targeting nanosystems are anticipated to play a significant role in the management of pancreatic cancer.

Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.

AIMS AND BACKGROUND: Hypercalcaemia due to metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour is challenging to manage and requires a multimodality approach. METHODS: We present a case of a woman undergoing liver transplantation for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour. RESULTS: A young woman with a history of parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour (Ki-67 5%) removed in 1998 developed bilobar liver metastases in 2004 and underwent repeated transarterial embolisations of liver tumour and therapy with somatostatin analogue. In view of symptomatic hypercalcaemia refractory to medical therapy, she underwent liver transplantation in 2006. In 2012, follow-up imaging showed a 3-cm hypervascular lesion in the posterior wall of the stomach, which was confirmed on endoscopic ultrasound and on gallium-68-octreotate positron emission tomography scan. A gastric wall resection was performed in February 2013, and biopsies showed a neuroendocrine tumour of intermediate grade (Ki-67 15%). In June 2013, a restaging imaging showed a 2.4 cm lesion in the left breast, which was reported as a primary breast cancer on biopsies, and a 14-mm tissue lesion anterior to the gastric antrum. The patient underwent surgical excision of the breast cancer followed by hormone treatment and radiotherapy. She had surgical removal of the gastric recurrence with adjuvant chemotherapy postoperatively. CONCLUSIONS: Hypercalcaemia related to parathyroid hormone-related peptide-secreting neuroendocrine tumour can be life-threatening, and liver transplantation may be a viable option in case of liver only diffuse neuroendocrine metastases refractory to other therapies. The risk of tumour recurrence remains a significant clinical problem after liver transplantation, and only a few patients might be considered tumour-free 5 years after liver transplantation.