Liver transplantation for isolated unresectable colorectal liver metastases - Protocol for a service evaluation in the United Kingdom - UKCoMET study.

BACKGROUND: Liver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation. METHODS: Opinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified. RESULTS: This paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described. CONCLUSION: This service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom.

A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID-19 pandemic.

INTRODUCTION: Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers. METHODS: Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD > 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019. RESULTS: The retrieval rate for deceased donor livers (71% vs. 54%; P < .0001) and conversion from offer to completed transplant (63% vs. 48%; P < .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort. CONCLUSIONS: We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

The effect of liver transplantation on patient-centred outcomes: a propensity-score matched analysis.

It is unclear whether liver transplantation confers an increase in health-related quality of life (HR-QoL) across all dimensions of health. This study aimed to estimate the effect of liver transplantation on HR-QoL. Pre- and post-transplantation patients attending an outpatient clinic were invited to complete the condition-specific 'Short form of liver disease QOL' questionnaire. Mixed-effect linear regression and propensity-score matching (PSM) on pretransplantation characteristics were used to estimate the difference in overall HR-QoL associated with transplantation. Of 454/609 (74.5%) eligible patients who were included in the analysis, 102 (22.5%) patients fall under pretransplantation category, and 352 (77.5%) were under post-transplantation category. Overall HR-QoL post-transplantation significantly increased in patients without hepatocellular carcinoma (HCC) (ß = 16.84, 95% CI: 13.33 to 20.35, P < 0.001), but not with HCC (ß = 1.25, 95% CI: -5.09 to 7.60, P = 0.704). Donation after circulatory death (DCD) organ recipients had a significantly lower HR-QoL (ß = -4.61, 95% CI: -8.95 to -0.24, P = 0.043). Following PSM, transplantation was associated with a significant increase in overall HR-QoL (average treatment effect: 6.3, 95% CI: 2.1-10.9). There is a significant improvement in HR-QoL attributable to transplantation in this cohort. Post-transplantation HR-QoL was affected by several factors, including HCC status and DCD transplantation, which has important implications for counselling prior to liver transplantation.

Quantifying changes in innate immune function following liver transplantation for chronic liver disease.

BACKGROUND: Liver transplantation (LT) offers patients with cirrhosis long-term survival, however many die from sepsis whilst awaiting LT. The liver's role in innate immunity may be key to improving outcomes, but the immune effects of LT have not been quantified. METHODS: Innate immune capacity was assessed by clearance of 99mTc-Albumin nanospheres in patients with chronic liver failure before and after LT. RESULTS: Twenty-eight patients with chronic liver disease on the LT waiting list entered the study during the twelve-month study period and nine patients underwent LT and completed the study protocol. One patient developed hepatic artery thrombosis in <7 days and was excluded from the study. Innate immune function was significantly impaired in patients with chronic liver disease on the LT waiting list and this was directly correlated with MELD score. LT normalised innate immune function by day 1 post LT with further improvement occurring by day 7 post LT. Donor liver weight was the only factor correlated with innate immune function at day 1 post LT but this effect was negated by day 7 post LT. CONCLUSION: Recognising the immune effects of LT may facilitate treatment of cirrhosis and inform development of extracorporeal liver support systems.

Impact of body mass index in liver transplantation for nonalcoholic fatty liver disease and alcoholic liver disease.

BACKGROUND: This study evaluates long-term outcomes and body mass index (BMI) following liver transplantation (LT) for non-alcoholic fatty liver disease (NAFLD) in comparison with alcoholic liver disease (ALD). METHODS: Patient and graft survival were compared using Kaplan Meier curves and log rank test. Multivariable analysis of recipient and donor characteristics was performed as determinants of patient survival. BMI at listing was compared with BMI post-LT. RESULTS: Patient survival at 1-, 3-, 5- and 10 years post-LT was similar in the ALD group (n = 195) compared with the NAFLD group (n = 84) (93% vs. 93%, 91% vs. 89%, 86% vs. 77%, 64% vs. 66% respectively, p = 0.21). One patient in the NAFLD group was re-transplanted and none in the ALD group therefore graft survival was also similar (p = 0.20). Multivariable analysis didn't identify any significant predictors of reduced survival. In comparison with the ALD group, BMI was significantly higher in the NAFLD group at listing (31 vs. 27, p < 0.001), 3-months post-LT (28 vs. 26, p < 0.05) and 6-months post-LT (29 vs. 27, p < 0.05) but was equivalent by 5-years post-LT (29 vs. 30, p = 0.80). CONCLUSIONS: NAFLD patients had similar patient and graft survival post-LT compared to ALD. NAFLD patients returned to listing BMI by one-year post-LT but by 5-years post-LT there was no difference in BMI between the groups.

Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study.

OBJECTIVE: To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score. BACKGROUND: POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance. METHODS: Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed. RESULTS: A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created. CONCLUSIONS: The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

Clinical Outcomes of Ablation Compared with Resection for Single Hepatocellular Carcinoma Lesions, as a Primary Treatment or Bridging to Liver Transplantation: A Retrospective Comparative Study.

BACKGROUND Ablative therapies (AT) are widely utilized as bridging treatment for liver transplantation (LT) candidates with hepatocellular carcinoma (HCC) who are on the transplant waiting list to minimize dropout rate. We aimed to investigate whether AT could be considered a primary treatment modality for LT candidates with single, small HCC lesions. MATERIAL AND METHODS We retrospectively investigated the outcomes of patients with AT for single HCC lesions as primary treatment or bridging to LT between 2010 and 2017, compared with surgical resection (SR) during the same time period as control. Univariate and multivariate survival analyses were performed. Matched analysis, after propensity score matching (PSM), was performed to minimize the selection bias confounding effect on outcomes. RESULTS Of 162 patients identified, 92 received AT and 70 had SR. PSM identified 38 paired matches in each group. Overall survival (OS) and disease-free survival (DFS) before matching showed comparable outcomes for each treatment after 1, 3, and 5 years. Multivariate analysis using Cox regression models adjusting the study confounders showed lesion size (>30 mm), not treatment received, was associated with worse DFS (hazard ratio, 2.21 [95% confidence interval, 1.14-4.28]). In the matched groups, OS and DFS were equivalent and consistent with the whole-cohort survival outcomes. Explant histopathology of patients having AT as a bridge to LT showed complete pathological response in 85.7% of patients. CONCLUSIONS This study supports the use of AT with curative intent for single ≤3-cm HCCs, particularly in LT candidates, with salvage transplantation kept as a backup in case of recurrence.

Laparoscopic liver resection in cirrhotics: feasibility and short-term outcomes compared to non-cirrhotics.

BACKGROUND: Laparoscopic liver resection (LLR) is increasingly common worldwide but its suitability in patients with cirrhosis is not clearly defined. There are minimal data in the western literature on this topic and previous work has compared LLR to open hepatectomy rather than to LLR in non-cirrhotic patients. This study compared short-term outcomes of LLR in cirrhotic patients to LLR in non-cirrhotic patients. METHODS: Retrospective review of minor LLR at the Royal Infirmary of Edinburgh from January 2006 to January 2018 was conducted. Patients were stratified by whether they had cirrhosis - defined as per radiological appearances and liver function tests. Variables of interest included baseline clinicopathological information with short-term outcomes (length of stay and complications) regarded as the primary outcome of interest. RESULTS: Out of 1207 liver resections in the study period, there were 120 LLR with 30 patients having cirrhosis. Patients with cirrhosis were more likely to be male and have higher median American Society of Anesthesiologists scores (3 versus 2; P < 0.01). The most common operation was left lateral sectionectomy (n = 67). There was no difference in duration of surgery (cirrhosis 88 min versus no cirrhosis 99 min; P = 0.64) and patients in the cirrhosis arm had no conversions to open (0% versus 12%; P = 0.06). There was no difference in complications (12% versus 13%; P = 0.75) or median length of stay (4 versus 4 days; P = 0.14) and no difference in survival between both groups. CONCLUSION: With careful patient selection, LLR is feasible in patients with cirrhosis and provides comparable outcomes to non-cirrhotic patients undergoing LLR.

Peritubular capillary rarefaction and lymphangiogenesis in chronic allograft failure.

BACKGROUND: Chronic renal allograft failure is a common and multifactorial but incompletely understood process with no effective treatment strategy. METHODS: We used immunohistochemistry to evaluate changes in density and turnover (proliferation) of the microvasculature and lymphatic vessels in endstage human transplant nephrectomies and control tissue derived from macroscopically normal areas of native nephrectomy specimens removed for renal carcinoma. We also examined the expression of angiogenic and lymphangiogenic growth factors in the associated inflammatory infiltrate. RESULTS: Endstage allografts showed reduced microvascular density in cortex and medulla compared with controls (P<0.0001), despite the presence of endothelial cell proliferation. However, the grafts also showed new lymphatic vessels in the tubulointerstitium, not evident in controls, and which appeared to be functional with luminal macrophages. Double labeling studies showed a subpopulation of the graft-infiltrating macrophages to be immunopositive for inducible nitric oxide synthase or vascular endothelial growth factor-C (a lymphatic-specific growth factor). B cells also strongly expressed the inflammatory and angiogenic cytokine vascular endothelial growth factor A. CONCLUSIONS: The present results identify contrasting changes in the microanatomy of vascular and lymphatic beds in endstage renal allografts associated with subpopulations of infiltrating macrophages and B cells that potentially regulate some of these changes. These cells and processes could become a new therapeutic target in chronic allograft failure.

Post-surgical Pancreatitis Masquerading as Recurrent Neuroendocrine Cancer.

Neuroendocrine tumours of the pancreas can have a spectrum of behaviour from relatively benign to aggressive. Resection can result in cure although metastatic disease is described. We present an unusual case of an apparent local recurrence of previously resected neuroendocrine tumour in a young man who had undergone distal pancreatectomy. Pathological analysis demonstrated focal post-surgical pancreatitis with radiological appearances bearing striking similarity to the original primary tumour.