Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.

Liver transplantation for HCC: validation of prognostic power of the RETREAT score for recurrence in a UK cohort.

BACKGROUND: The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC. METHODS: LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria. RESULTS: 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively). CONCLUSION: LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.

Meta-analysis of warmed versus standard temperature CO2 insufflation for laparoscopic cholecystectomy.

BACKGROUND: There is conflicting evidence for the use of warmed, humidified carbon dioxide (CO2) for creating pneumoperitoneum during laparoscopic cholecystectomy. Few studies have reported less post-operative pain and analgesic requirement when warmed CO2 was used. AIM: This systematic review and meta-analysis aims to analyse the literature on the use of warmed CO2 in comparison to standard temperature CO2 during laparoscopic cholecystectomy. METHODS: Systematic review and meta-analysis carried out in line with the PRISMA guidelines. Primary outcomes of interest were post-operative pain at 6 h, day 1 and day 2 following laparoscopic cholecystectomy. Secondary outcomes were analgesic usage and drop in intra-operative core body temperature. Standard Mean Difference (SMD) was calculated for continuous variables. RESULTS: Six randomised controlled trials (RCTs) met the inclusion criteria (n = 369). There was no significant difference in post-operative pain at 6 h [3 RCTs; SMD = -0.66 (-1.33, 0.02) (Z = 1.89) (P = 0.06)], day 1 [4 RCTs; SMD = -0.51 (-1.47, 0.44) (Z = 1.05) (P = 0.29)] and day 2 [2 RCTs; SMD = -0.96 (-2.30, 0.37) (Z = 1.42) (P = 0.16)] between the warmed CO2 and standard CO2 group. There was no difference in analgesic usage between the two groups, but pooled analysis was not possible. Two RCTs reported significant drop in intra-operative core body temperature, but there were no adverse events related to this. CONCLUSIONS: This review showed no difference in post-operative pain and analgesic requirements between the warmed and standard CO2 insufflation during laparoscopic cholecystectomy. Currently there is not enough high quality evidence to suggest routine usage of warmed CO2 for creating pneumoperitoneum during laparoscopic cholecystectomy.

A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD). METHODS: Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site. RESULTS: Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group. CONCLUSIONS: Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

Point-of-care device for the noninvasive assessment of hepatic macrosteatosis in liver donors.

BACKGROUND: Quantification of macrosteatosis (MS) in the liver is important given that it has shown to directly correlate with adverse post-liver transplant (LT) outcomes. With advances in medical technology and an implicit understanding of pathology, noninvasive methods of quantitatively assessing MS are in various stages of development. Each of these methods is based on the physical principles of differences between a fat-laden hepatocyte and a normal one. METHODS: In this regard, after a proof-of-concept study on a prototype for a simple, real-time, handheld device using the principle of diffuse reflectance spectroscopy, this study presents an upgraded point-of-care (POC) device for the noninvasive assessment of hepatic MS in liver donors. RESULTS: The device was validated on cohort of donor livers and showed a sensitivity (0.0021 V/% fat) and highly correlated (r = 0.9868, P < .0001) with gold-standard liver biopsy. Results showed that this upgraded POC device provides a reliable method for the noninvasive assessment of hepatic MS, which is crucial for selecting suitable donor livers for LT. CONCLUSION: The device has the potential to be an invaluable apparatus at the hands of the organ-retrieving surgeon. It is noninvasive, portable (handheld), and economic; provides real-time readings of the percentage of MS; and can be efficaciously handled by any member of the organ-retrieving team.

Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom.

Obesity levels in the United Kingdom have risen over the years. Studies from the United States and elsewhere have reported variable outcomes for obese liver transplant recipients in terms of post-liver transplant morbidity, mortality, and graft survival. This study was designed to analyze the impact of the body mass index (BMI) on outcomes following adult liver transplantation. Data from 1994 to 2009 were retrieved from a prospectively maintained database. Patients were stratified into 5 World Health Organization BMI categories: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), obese (30.0-34.9 kg/m(2)), and morbidly obese (≥35.0 kg/m(2)). The primary outcome was an evaluation of graft and patient survival, and the secondary outcome was an assessment of postoperative morbidity. Bonferroni correction was applied with statistical significance set at P < 0.012. Kaplan-Meier curves were used to study the effects of BMI on graft and patient survival. A total of 1325 patients were included in the study: underweight (n = 47 or 3.5%), normal-weight (n = 643 or 48.5%), overweight (n = 417 or 31.5%), obese (n = 145 or 10.9%), and morbidly obese patients (n = 73 or 5.5%). The rate of postoperative infective complications was significantly higher in the overweight (60.7%, P < 0.01) and obese recipients (65.5%, P < 0.01) versus the normal-weight recipients (50.4%). The morbidly obese patients had a longer mean intensive care unit (ICU) stay than the normal-weight patients (4.7 versus 3.2 days, P = 0.03). The mean hospital stay was longer for the overweight (22.4 days, P < 0.001), obese (21.3 days, P = 0.04), and morbidly obese recipients (22.4 days, P = 0.047) versus the normal-weight recipients (18.0 days). There was no difference in death-censored graft survival or patient survival between the groups. In conclusion, this is the largest and only reported UK series on BMI and outcomes following liver transplantation. Overweight and obese patients have significantly increased morbidity in terms of infective complications after liver transplantation and, consequently, longer ICU and hospital stays.

Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation?

BACKGROUND: In cirrhotic patients with hepatocellular carcinoma (HCC), poor differentiation in pre-liver transplantation (LT) biopsy of the largest tumour is used as a criterion for exclusion from LT in some centres. The potential role of pre-LT biopsy at one centre was explored. METHODS: A prospective database of patients undergoing orthotopic LT for radiologically diagnosed HCC at St James's University Hospital, Leeds during 2006-2011 was analysed. RESULTS: A total of 60 predominantly male (85.0%) patients with viral hepatitis were identified. There were discrepancies between radiological and histopathological findings with respect to the number of tumours identified (in 27 patients, 45.0%) and their size (in 63 tumours, 64.3%). In four (6.7%) patients, the largest lesion, which would theoretically have been targeted for biopsy, was not the largest in the explant. Nine (31.0%) patients with multifocal HCC had tumours of differing grades. In two (6.9%) patients, the largest tumour was well differentiated, but smaller tumours in the explant were poorly differentiated. In one patient, the largest lesion was benign and smaller invasive tumours were confirmed histologically. CONCLUSIONS: The need to optimize selection for LT in HCC remains. In the present series, the largest tumour was not always representative of overall tumour burden or biological aggression and its potential use to exclude patients from LT is questionable.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease: A retrospective observational study.

BACKGROUND: Children with acute liver failure (ALF) who meet the criteria are eligible for super-urgent transplantation, whereas children with end-stage chronic liver disease (ESCLD) are usually transplanted electively. Pediatric liver trans plantation (PLT) in ALF and ESCLD settings has been well described in the literature, but there are no studies comparing the outcomes in these two groups. AIM: To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT. METHODS: This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019. ALF and ESCLD groups were compared for pretransplant recipient, donor and operative parameters, and post-operative outcomes including graft and patient survival. RESULTS: Over a 20-year study period, 232 primary PLTs were performed at our center; 195 were transplanted for ESCLD and 37 were transplanted for ALF. The ALF recipients were significantly older (median 8 years vs 5.4 years; P = 0.031) and heavier (31 kg vs 21 kg; P = 0.011). Living donor grafts were used more in the ESCLD group (34 vs 0; P = 0.006). There was no difference between the two groups concerning vascular complications and rejection, but there were more bile leaks in the ESCLD group. Post-transplant patient survival was significantly higher in the ESCLD group: 1-, 5-, and 10-year survival rates were 97.9%, 93.9%, and 89.4%, respectively, compared to 78.3%, 78.3%, and 78.3% in the ALF group (P = 0.007). However, there was no difference in 1-, 5-, and 10-year graft survival between the ESCLD and ALF groups (90.7%, 82.9%, 77.3% vs 75.6%, 72.4%, and 66.9%; P = 0.119). CONCLUSION: Patient survival is inferior in ALF compared to ESCLD recipients; the main reason is death in the 1st year post-PLT in ALF group. Once the ALF children overcome the 1st year after transplant, their survival stabilizes, and they have good long-term outcomes.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

Portal vein embolization versus dual vein embolization for management of the future liver remnant in patients undergoing major hepatectomy: meta-analysis.

BACKGROUND: This meta-analysis aimed to compare progression to surgery, extent of liver hypertrophy, and postoperative outcomes in patients planned for major hepatectomy following either portal vein embolization (PVE) or dual vein embolization (DVE) for management of an inadequate future liver remnant (FLR). METHODS: An electronic search was performed of MEDLINE, Embase, and PubMed databases using both medical subject headings (MeSH) and truncated word searches. Articles comparing PVE with DVE up to January 2022 were included. Articles comparing sequential DVE were excluded. ORs, risk ratios, and mean difference (MD) were calculated using fixed and random-effects models for meta-analysis. RESULTS: Eight retrospective studies including 523 patients were included in the study. Baseline characteristics between the groups, specifically, age, sex, BMI, indication for resection, and baseline FLR (ml and per cent) were comparable. The percentage increase in hypertrophy was larger in the DVE group, 66 per cent in the DVE group versus 27 per cent in the PVE group, MD 39.07 (9.09, 69.05) (P = 0.010). Significantly fewer patients failed to progress to surgery in the DVE group than the PVE group, 13 per cent versus 25 per cent respectively OR 0.53 (0.31, 0.90) (P = 0.020). Rates of post-hepatectomy liver failure 13 per cent versus 22 per cent (P = 0.130) and major complications 20 per cent versus 28 per cent (Clavien-Dindo more than IIIa) (P = 0.280) were lower. Perioperative mortality was lower with DVE, 1 per cent versus 10 per cent (P = 0.010). CONCLUSION: DVE seems to produce a greater degree of hypertrophy of the FLR than PVE alone which translates into more patients progressing to surgery. Higher quality studies are needed to confirm these results.

Late-Onset Peripheral T-Cell Lymphoma Not Otherwise Specified in a Liver Transplant Recipient: A Rare Subtype of Posttransplant Lymphoproliferative Disorder.

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication seen in the period after liver transplant. The commonest subtype is B-cell PTLD which is usually associated with Epstein-Barr virus (EBV) infection. T-cell PTLD is rare and the association with EBV is again rarer. CASE: Our patient, a 21-year-old young adult, presented to us with generalized lymphadenopathy, 5 years after liver transplantation. The biopsy of the lymph node was suggestive of peripheral T-cell lymphoma not otherwise specified, which was associated with EBV infection. The Positron emission tomography and computerised tomography (PET-CT) scan showed stage 3 disease. He was treated with standard cyclophosphamide, doxorubicin, etoposide, vincristine, and prednisolone chemotherapy and is currently in remission. CONCLUSION: Peripheral T-cell lymphoma not otherwise specified is a rare subtype of PTLD and its association with EBV is even more rare. A few patients can achieve complete remission with standard chemotherapy.

Awareness and Concerns Among Adult Liver Transplant Recipients in the Current Pandemic Caused by Novel Coronavirus (COVID-19): Strategies to Safeguard a High-risk Population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and there are obvious concerns for the immunocompromised patient population including transplant recipients. Creating awareness and understanding patient concerns will play an important role in protecting this vulnerable group in developing timely and appropriate healthcare interventions. METHODS: A cross-sectional online survey was conducted between 23rd March 2020 and 1st April 2020 among 154 liver transplant recipients, transplanted between October 2018 and February 2020. An 18-point questionnaire explored their knowledge of COVID-19, awareness of recipient's high-risk status, interventions to minimize cross-infections, and concerns of this patient group regarding the pandemic. RESULTS: There were 112 (73%) respondents, with median age of 53 years (81% males). There was no difference in demographics between those who responded (n = 112) and those who did not respond to the survey (n = 42). Most of the recipients were aware of the main symptoms of COVID-19, such as fever (92%), breathlessness (86%), and dry cough (87%), but less than half were aware of diarrhea (39%) as a symptom. Awareness about spread from asymptomatic individuals was limited (26%). Majority (95%) understood their high-risk status, but worryingly, 23% of the respondents felt that there was no risk in visiting the hospital for routine clinic visit and blood tests. Concerns were raised by the recipients mostly regarding the uncertainties of COVID-19 infection and its treatment options, the quality of information on social messaging platforms, and lack of access to routine tests/immunosuppression levels because of lockdown/social distancing. CONCLUSIONS: Our liver transplant recipients have a reasonable awareness regarding COVID-19. Problems in accessing the healthcare system during prolonged periods of lockdown was a major concern. It is important for each transplant unit to educate, support, and remain accessible to this vulnerable patient cohort as the pandemic continues to progress worldwide.

Trinational Study Exploring the Early Impact of the COVID-19 Pandemic on Organ Donation and Liver Transplantation at National and Unit Levels.

BACKGROUND: The coronavirus disease (COVID-19) pandemic is stressing healthcare services to an unprecedented extent. There is anecdotal evidence of reduction in organ donation and transplantation activity across the world. METHODS: The weekly organ donation and liver transplant numbers over a 3-month period (Feb 17, 2020, till May 17, 2020) for the United States, United Kingdom, and India were compared with their previous year's activity. Liver transplant activity in 6 centers from these countries with varying local COVID-19 caseload was also compared. RESULTS: The COVID-19 pandemic has led to a significant contraction in organ donation and liver transplantation in all 3 countries. Peak reduction ranged from 25% in the United States to over 80% in the United Kingdom and India. The reduction was different for deceased donor and living donor liver transplantation and varied between centers within a country. There was early evidence of recovery of deceased donation in the United States and United Kingdom and resumption of living donor liver transplantation activity in India toward the end of the study period. A number of policy changes were undertaken at national and transplant center levels to ensure safe transplantation despite significant redirection of resources to combat the pandemic. CONCLUSIONS: There was a substantial reduction in organ donation and liver transplantation activity across the 3 countries with signs of recovery toward the end of the study period. Multiple factors including COVID-19 severity, stress on resources and influence of regulatory agencies and local factors are responsible for the reduction and recovery.

The feasibility of percutaneous transradial coronary intervention for saphenous vein graft lesions and comparison with transfemoral route.

BACKGROUND: Transradial PCI is rapidly expanding and is effective in complex lesion subset due to miniaturization of devices and accumulated clinical experience. However, the femoral route still remains the usual vascular route used for SVG PCI in most catheterization laboratories. METHODS: We examined 115 consecutive patients undergoing SVG PCI between January 2003 and December 2005 and compared the radial (51 patients) and femoral (64 patients) approaches. RESULTS: Baseline demographics, lesion location, and clinical indication were similar in both groups. GpIIbIIIa inhibitor usage was high in the radial group (78.4% vs. 53.1%, P < 0.01). Angiographic success was similar in both groups, 96% in the radial group vs. 96.8 in the femoral. Total fluoroscopy time (18.59 +/- 12.23 vs. 20.45 +/- 12.9), total procedure time (52.1 +/- 29.5 vs. 43.90 +/- 23.31 min), and the use of total contrast volume (357.0 +/- 174.0 vs. 346.0 +/- 157.0 ml) were similar in the radial and femoral groups, respectively. In-hospital MACE (radial: 2 MI [4.0%] vs. femoral: 1 death [1.6%] and 7 MI [11.0%], P < 0.01) were similar in both groups. Access site vascular complications (radial: 2 [4.0%] vs. femoral: 10 [11.0%], P < 0.001) were significantly less in the radial group. CONCLUSIONS: The transradial approach for SVG PCI is feasible, safe, and as quick as the femoral approach. Procedural success is high with similar radiation and contrast exposure. In-hospital MI in the femoral group is high because of more-unstable patients. However, there are significantly lower vascular complications despite high use of platelet inhibitors in the radial approach.

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review.

BACKGROUND: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. AIM: To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. METHODS: Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. RESULTS: 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group. CONCLUSIONS: There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.

Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy.

Hepatic portal venous gas (HPVG) in most cases signifies either mechanical migration of air into the portal system due to bowel ischaemia (pneumatosis intestinalis) or portal sepsis due to gas-forming organisms. Successful management of portal sepsis involves early identification of the condition, intensive resuscitation, broad-spectrum antibiotics and a laparotomy for possible bowel ischaemia. In this report, we discuss the case of a patient with pneumatosis intestinalis and HPVG after an elective laparoscopic right hemicolectomy. After an initial slow recovery, on postoperative day seven, the patient had profuse diarrhoea and confusion, and was hyponatraemic. A CT scan revealed pneumatosis intestinalis and HPVG. A laparotomy showed no obvious cause for HPVG and there was no ischaemic bowel. She was managed with intensive care, hyperbaric oxygen therapy, broad-spectrum antibiotics and total-parenteral nutrition. She has made a good recovery. This case highlights the presenting features, differential diagnoses, and management of pneumatosis intestinalis and HPVG.