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Neuroendocrine liver metastases (LM-NEN) develop in a considerable proportion of patients with gastroenteropancreatic neuroendocrine neoplasms. There is a paucity of experimental models that accurately recapitulate this complex metastatic... more
Neuroendocrine liver metastases (LM-NEN) develop in a considerable proportion of patients with gastroenteropancreatic neuroendocrine neoplasms. There is a paucity of experimental models that accurately recapitulate this complex metastatic human liver microenvironment precluding scientific and clinical advancements. Here, we describe the development of a novel personalised immunocompetent precision cut tumour slice (PCTS) model for LM-NEN using resected human liver tissue. The histological assessment throughout the culture demonstrated that slices maintain viability for at least 7 days and retain the cellular heterogeneity of the original tumour. Essential clinical features, such as patient-specific histoarchitecture, tumour grade, neuroendocrine differentiation and metabolic capacity, are preserved in the slices. The PCTS also replicate the tumor-specific immunological profile as shown by the innate and adaptive immunity markers analysis. Furthermore, the study of soluble immune che...
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The “gut homing” hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut‐derived T cells to the liver. However,... more
The “gut homing” hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut‐derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine “the gut homing theory” in patients with PSC with associated inflammatory bowel disease (PSC‐IBD) and across multiple inflammatory liver diseases.
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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... more
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.
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Background: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and easily removable due... more
Background: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and easily removable due to long retrieval wires deployed within the duodenum. Methods: 62 patients who had this stent inserted were prospectively analysed. Results: 81% of patients had long-term resolution of their stricture with a significant improvement in liver function tests. Complication rates were 15% with one patient requiring biliary reconstruction. Conclusions: This type of FCSEMS is effective and safe at resolving anastomotic strictures.
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Thyroid hormones are regarded as the major controllers of metabolic rate and oxygen consumption in mammals. Although it has been demonstrated that thyroid hormone supplementation improves bovine embryo development in vitro, the cellular... more
Thyroid hormones are regarded as the major controllers of metabolic rate and oxygen consumption in mammals. Although it has been demonstrated that thyroid hormone supplementation improves bovine embryo development in vitro, the cellular mechanisms underlying these effects are so far unknown. In this study, we investigated the role of thyroid hormone in development of human preimplantation embryos. Embryos were cultured in the presence or absence of 10−7 M triiodothyronine (T3) till blastocyst stage. Inner cell mass (ICM) and trophectoderm (TE) were separated mechanically and subjected to RNAseq or quantification of mitochondrial DNA copy number. Analyses were performed using DESeq (v1.16.0 on R v3.1.3), MeV4.9 and MitoMiner 4.0v2018 JUN platforms. We found that the exposure of human preimplantation embryos to T3 had a profound impact on nuclear gene transcription only in the cells of ICM (1178 regulated genes—10.5% of 11 196 expressed genes) and almost no effect on cells of TE (38 r...
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Background and Aims: Patients with liver tumors involving the inferior vena cava have a poor outcome without surgery. Liver resection en bloc with inferior vena cava resection and reconstruction is now performed in many centers. The... more
Background and Aims: Patients with liver tumors involving the inferior vena cava have a poor outcome without surgery. Liver resection en bloc with inferior vena cava resection and reconstruction is now performed in many centers. The purpose of this study is to investigate the safety and efficacy of inferior vena cava reconstruction during hepatic resection. Materials and Methods: A review of 12 centers reporting 240 patients with combined hepatectomy and inferior vena cava resection and reconstruction for malignant tumors was performed. Sample size, patient characteristics, histological type of the tumor, method of reconstruction, complications, and long-term survival (1-, 2-, and 5-year survival) were evaluated. Results: A total of 240 patients from 12 institutions (male 58%) with mean age 54 years underwent combined liver resection and inferior vena cava resection and reconstruction for colorectal liver metastases (43%), cholangiocarcinomas (26%), hepatocellular carcinomas (19%), ...
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Research Interests: Adolescent, Medicine, Biopsy, Humans, Liver, and 15 moreFemale, Immunosuppression, Liver Transplantation, Prednisolone, Allografts, Ammonia, Clinical Sciences, Hepatic Encephalopathy, Adult, Acetaminophen, Graft Rejection, Portal vein, Orthotopic Liver Transplantation, Immunosuppressive Agents, and Hepatectomy
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Research Interests: Surgery, Survival Analysis, Organ Donation, Medicine, Transplantation, and 15 moreHumans, Survivors, Female, Male, Liver Transplantation, Cadaver, Aged, Middle Aged, Retrospective Studies, Sudden Cardiac Death, Machine Perfusion, Heart Diseases, Reoperation, Cause of death, and Medical and Health Sciences
Background : Hepatocellular carcinoma (HCC) is ranked as the sixth most common solid cancer and the third leading cause of cancer-related death in the world. Sorafenib is the first line systematic treatment for patients with advanced HCC.... more
Background : Hepatocellular carcinoma (HCC) is ranked as the sixth most common solid cancer and the third leading cause of cancer-related death in the world. Sorafenib is the first line systematic treatment for patients with advanced HCC. Hepatic arterial infusion chemotherapy（HAIC）has been proved to be an effective treatment for advanced HCC. Here, we conducted a meta-analysis to compared the efficacy of HAIC versus sorafenib of advanced HCC patients with PVTT. Methods : The databases of MEDLINE (PubMed), Cochrane Library, EMBASE, and Web of Science were systematically searched for retrieving the relevant publications before 31 July 2019. The endpoint included overall survival (OS), time to progression (TTP), partial response rate (PRR), complete response rate (CRR), objective response rate (ORR), stable disease rate (SDR). Results : A total of three studies involving 214 advanced HCC patients with PVTT enrolled in this meta-analysis. HAIC significantly improved TTP (hazard ratio (...
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Here, we describe a case of occlusive hepatic artery thrombus in a liver procured from an 18-year-old deceased donor after circulatory death. The donor had died of multiple trauma following a road traffic collision. Occlusive thrombus was... more
Here, we describe a case of occlusive hepatic artery thrombus in a liver procured from an 18-year-old deceased donor after circulatory death. The donor had died of multiple trauma following a road traffic collision. Occlusive thrombus was found at the hepatic artery bifurcation during back-table preparation. Consequently, the liver transplant did not proceed. We suggest careful assessment of hepatic arteries of all donor livers before transplant, particularly those from donors who are involved in deceleration injuries. Transplanting such livers may lead to primary nonfunction.
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The outcome of treatment for advanced hepatoblastoma has recently improved after the introduction of preoperative or pre- and postoperative cisplatin-containing chemotherapy combined with complete surgical excision. The role of liver... more
The outcome of treatment for advanced hepatoblastoma has recently improved after the introduction of preoperative or pre- and postoperative cisplatin-containing chemotherapy combined with complete surgical excision. The role of liver transplantation in a population of patients who have received this regimen has not been clearly defined. Orthotopic liver transplantation (OLT) was performed in 13 children, aged 5 months to 11 years (median 27 months), who were assessed with unresectable hepatoblastoma, and whose pretreatment extent-of-disease was based on radiologic findings of group III (n=11) and group IV (n=2). One child with a multifocal tumor showed pulmonary metastases at presentation, but, according to radiologic studies, the deposits resolved with chemotherapy before liver transplantation. One other child showed exophytic extension of the primary tumor infiltrating the porta hepatis and body of the pancreas. All 13 patients received preoperative chemotherapy to reduce the size of the primary tumor(s) and to treat metastatic spread. Twelve children underwent elective OLT; all are alive and show normal graft function at a mean follow-up of 33 months (range 1-108). One child shows evidence of recurrent disease in the form of pulmonary metastases. One child underwent emergency OLT for acute liver failure after (incomplete) extended right hepatectomy and died from respiratory failure, with no evidence of recurrent tumor 3 weeks posttransplant. Liver transplantation is an effective treatment for unresectable unifocal or multifocal hepatoblastoma confined to the liver. A multidisciplinary approach to the management of hepatoblastoma, with thoughtful collaboration between pediatric oncologists, hepatologists, and liver surgeons, is essential.