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Article ; Online: Surgical management, including the role of transplantation, for intrahepatic and peri-hilar cholangiocarcinoma.

Malik, Abdullah K / Davidson, Brian R / Manas, Derek M

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2024 , Page(s) 108248

Abstract: Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious ... ...

Abstract	Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2024.108248
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Article ; Online: An invited commentary on "incisional hernia after liver transplantation: Risk factors, management strategies and long-term outcomes of a cohort study".

Lykoudis, Panagis M / Davidson, Brian R

International journal of surgery (London, England)

2020 Volume 80, Page(s) 40

MeSH term(s)	Cohort Studies ; Humans ; Incisional Hernia ; Liver Transplantation ; Risk Factors ; Time Factors
Language	English
Publishing date	2020-06-20
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2212038-5
ISSN	1743-9159 ; 1743-9191
ISSN (online)	1743-9159
ISSN	1743-9191
DOI	10.1016/j.ijsu.2020.06.020
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Article ; Online: Current postoperative nutritional practice after pancreatoduodenectomy in the UK: national survey and snapshot audit.

Halle-Smith, James M / Pathak, Samir / Frampton, Adam / Pandanaboyana, Sanjay / Sutcliffe, Robert P / Davidson, Brian R / Smith, Andrew M / Roberts, Keith J

BJS open

2024 Volume 8, Issue 2

MeSH term(s)	Humans ; Pancreaticoduodenectomy ; Practice Patterns, Physicians' ; Medical Audit ; United Kingdom
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrae021
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Article ; Online: Assessing the Impact of Primary Tumour Location on Survival After Resection of Colorectal Liver Metastases: A Propensity Weighted Retrospective Cohort Study.

Borakati, Aditya / Froghi, Farid / Shetye, Alysha / Fusai, Giuseppe K / Davidson, Brian R / Mirnezami, Reza

World journal of surgery

2022 Volume 46, Issue 7, Page(s) 1734–1755

Abstract: Background: Right-sided colonic tumours appear to have poorer survival after resection of colorectal liver metastases, although this may be confounded by various factors including advanced stage and emergency presentation.: Methods: Medical records ... ...

Abstract	Background: Right-sided colonic tumours appear to have poorer survival after resection of colorectal liver metastases, although this may be confounded by various factors including advanced stage and emergency presentation. Methods: Medical records of consecutive patients undergoing resection of colorectal liver metastases at a single centre from 2008 to 2015 were retrospectively reviewed. Cases were categorised by primary tumour location (right colon, left colon, rectum). Each primary location was weighted using propensity scores to balance covariates, including staging and mode of presentation. Cox regression was then applied to derive multivariable hazard ratios (HR) of survival after liver resection. Primary outcomes were 10-year overall survival (OS) and 5-year disease-free survival (DFS) after liver resection based on PTL. Results: 414 patients were included in the analysis. Left colonic tumours were significantly associated with higher rates of bilobar liver metastasis (36.2% vs. 20.1% and 30.1%) and larger maximum size of liver metastases compared with rectal and right-sided tumours, respectively. There was no difference in rates of extra-hepatic metastases, recurrence in the liver after resection or RAS, BRAF or p53 mutational status. After propensity weighting and Cox-regression, right-sided tumours were independently associated with significantly reduced 10 year OS (HR 1.56, 95% CI 1.03-2.36, p = 0.04) but not 5 year DFS (HR 1.36, 95% CI 0.89-2.08, p = 0.15). Conclusions: Compared with left colonic and rectal tumours, right-sided colonic tumours are independently associated with inferior OS after resection of CRLM. This is despite higher rates of bilobar liver metastases and larger metastases with left-sided tumours.
MeSH term(s)	Colonic Neoplasms/surgery ; Colorectal Neoplasms/pathology ; Hepatectomy ; Humans ; Liver Neoplasms/secondary ; Prognosis ; Retrospective Studies
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	224043-9
ISSN	1432-2323 ; 0364-2313
ISSN (online)	1432-2323
ISSN	0364-2313
DOI	10.1007/s00268-022-06514-z
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Article ; Online: Ex Vivo Perfusion of Porcine Pancreas and Liver Sourced from Commercial Abattoirs after Circulatory Death as a Research Resource: A Methodological Study.

Rai, Zainab L / Magbagbeola, Morenike / Doyle, Katie / Lindenroth, Lukas / Dwyer, George / Gander, Amir / Stilli, Agostino / Stoyanov, Danail / Davidson, Brian R

Methods and protocols

2023 Volume 6, Issue 4

Abstract: Background: Machine perfusion (MP) is increasingly used for human transplant organ preservation. The use of MP for research purposes is another opportunity for this technology. The porcine pancreas and liver are similar in anatomical size and function ... ...

Abstract	Background: Machine perfusion (MP) is increasingly used for human transplant organ preservation. The use of MP for research purposes is another opportunity for this technology. The porcine pancreas and liver are similar in anatomical size and function to their human counterparts, making them an excellent resource for research, but they have some important differences from human organs which can influence their research use. In this paper, we describe a technique developed and tested for the retrieval of porcine organs for use in research on perfused viable organs. Methods: Whole-organ porcine pancreata and livers were harvested at a commercial abattoir, following standard slaughterhouse processes. The standard slaughterhouse process involved a thoracotomy and mid-line laparotomy, and all the thoracoabdominal organs were removed. The pancreas, fixed in the retroperitoneum, was carefully dissected from its attachments to the surrounding structures, and tissue planes between the pancreas, spleen, duodenum, and colon were meticulously identified and dissected. Vessel exposure and division: The aorta, portal vein (PV), hepatic vein (HV), and hepatic artery (HA) were dissected and isolated, preserving the input and output channels for the liver and pancreas. A distal 3 cm of the aorta was preserved and divided and served as the input for the pancreas perfusions. The liver, PV, HV, and HA were preserved and divided to preserve the physiological channels of the input (PV and HA) and output (HV) for the liver perfusions. The porcine hepatic and pancreas anatomy shares significant resemblance with the gross anatomy found in humans, and this was taken into consideration when designing the perfusion circuitry. The porcine pancreas and spleen shared a common blood supply, with branches arising from the splenic artery. The organs were flushed with cold, heparinised normal saline and transported in a temperature-regulated receptacle maintained at a core temperature between 4 and 8 °C, in line with the standards of static cold storage (SCS), to a dedicated perfusion lab and perfused using our novel perfusion machine with autologous, heparinised porcine blood, also collected at the abattoir.
Language	English
Publishing date	2023-07-12
Publishing country	Switzerland
Document type	Journal Article
ISSN	2409-9279
ISSN (online)	2409-9279
DOI	10.3390/mps6040066
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Article ; Online: Recipient body mass index and infectious complications following liver transplantation.

Diaz-Nieto, Rafael / Lykoudis, Panagis M / Davidson, Brian R

HPB : the official journal of the International Hepato Pancreato Biliary Association

2019 Volume 21, Issue 8, Page(s) 1032–1038

Abstract: Background: Nutritional problems are common in patients requiring liver transplantation. Recipient obesity or malnutrition are thought to increase postoperative complications. Body mass index (BMI) is commonly used prior to major surgery but its value ... ...

Abstract	Background: Nutritional problems are common in patients requiring liver transplantation. Recipient obesity or malnutrition are thought to increase postoperative complications. Body mass index (BMI) is commonly used prior to major surgery but its value specifically in liver transplant assessment has not been established. This is a retrospective study assessing the correlation between the BMI of individuals undergoing liver transplant and the development of postoperative infectious complications. Methods: Data were collected from a prospectively maintained database regarding all consecutive patients over a period of 23 years. Preoperative recipient BMI was correlated with the number, nature and outcome of postoperative infective complications. Results: Of a total of 1156 consecutive patients, 13.2% developed infectious complications. Thirty-day mortality was 7.2% and 90-day mortality was 10%. Higher BMI was associated with higher risk of infections (p = 0.002). Wound infections occurred predominantly in obese patients (p = 0.001) while other types of infections were more common in malnourished patients (p < 0.001). Conclusion: Extremes of BMI are associated with increased infectious complications following liver transplantation. Patients with lower BMI had a higher rate of overall infectious complications whereas those with a higher BMI had increased general and wound complications.
MeSH term(s)	Adult ; Bacteremia/etiology ; Bacteremia/mortality ; Body Mass Index ; Cause of Death ; Databases, Factual ; Female ; Graft Rejection ; Humans ; Incidence ; Kaplan-Meier Estimate ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Male ; Middle Aged ; Obesity/complications ; Obesity/epidemiology ; Postoperative Complications/mortality ; Postoperative Complications/physiopathology ; Preoperative Period ; Prognosis ; Retrospective Studies ; Risk Assessment ; Statistics, Nonparametric ; Surgical Wound Infection/mortality ; Surgical Wound Infection/physiopathology ; Transplant Recipients
Language	English
Publishing date	2019-02-01
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2019.01.002
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Article: Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy.

Rai, Zainab L / Feakins, Roger / Pallett, Laura J / Manas, Derek / Davidson, Brian R

Journal of clinical medicine

2021 Volume 10, Issue 8

Abstract: Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a ... ...

Abstract	Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.
Language	English
Publishing date	2021-04-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10081609
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Article ; Online: Mitochondrial respiratory chain and Krebs cycle enzyme function in human donor livers subjected to end-ischaemic hypothermic machine perfusion.

Abudhaise, Hamid / Taanman, Jan-Willem / DeMuylder, Peter / Fuller, Barry / Davidson, Brian R

PloS one

2021 Volume 16, Issue 10, Page(s) e0257783

Abstract: Introduction: Marginal human donor livers are highly susceptible to ischaemia reperfusion injury and mitochondrial dysfunction. Oxygenation during hypothermic machine perfusion (HMP) was proposed to protect the mitochondria but the mechanism is unclear. ...

Abstract	Introduction: Marginal human donor livers are highly susceptible to ischaemia reperfusion injury and mitochondrial dysfunction. Oxygenation during hypothermic machine perfusion (HMP) was proposed to protect the mitochondria but the mechanism is unclear. Additionally, the distribution and uptake of perfusate oxygen during HMP are unknown. This study aimed to examine the feasibility of mitochondrial function analysis during end-ischaemic HMP, assess potential mitochondrial viability biomarkers, and record oxygenation kinetics. Methods: This was a randomised pilot study using human livers retrieved for transplant but not utilised. Livers (n = 38) were randomised at stage 1 into static cold storage (n = 6), hepatic artery HMP (n = 7), and non-oxygen supplemented portal vein HMP (n = 7) and at stage 2 into oxygen supplemented and non-oxygen supplemented portal vein HMP (n = 11 and 7, respectively). Mitochondrial parameters were compared between the groups and between low- and high-risk marginal livers based on donor history, organ steatosis and preservation period. The oxygen delivery efficiency was assessed in additional 6 livers using real-time measurements of perfusate and parenchymal oxygen. Results: The change in mitochondrial respiratory chain (complex I, II, III, IV) and Krebs cycle enzyme activity (aconitase, citrate synthase) before and after 4-hour preservation was not different between groups in both study stages (p > 0.05). Low-risk livers that could have been used clinically (n = 8) had lower complex II-III activities after 4-hour perfusion, compared with high-risk livers (73 nmol/mg/min vs. 113 nmol/mg/min, p = 0.01). Parenchymal pO2 was consistently lower than perfusate pO2 (p ≤ 0.001), stabilised in 28 minutes compared to 3 minutes in perfusate (p = 0.003), and decreased faster upon oxygen cessation (75 vs. 36 minutes, p = 0.003). Conclusions: Actively oxygenated and air-equilibrated end-ischaemic HMP did not induce oxidative damage of aconitase, and respiratory chain complexes remained intact. Mitochondria likely respond to variable perfusate oxygen levels by adapting their respiratory function during end-ischaemic HMP. Complex II-III activities should be further investigated as viability biomarkers.
MeSH term(s)	Aged ; Citric Acid Cycle/drug effects ; Citric Acid Cycle/genetics ; Electron Transport/genetics ; Electron Transport/physiology ; Female ; Hepatic Artery/metabolism ; Hepatic Artery/pathology ; Humans ; Hypothermia, Induced/methods ; Liver/metabolism ; Liver/pathology ; Liver Transplantation/adverse effects ; Living Donors ; Male ; Middle Aged ; Organ Preservation/methods ; Organ Preservation Solutions/pharmacology ; Oxygen/administration & dosage ; Perfusion/methods ; Pilot Projects ; Portal Vein/metabolism ; Portal Vein/pathology ; Reperfusion Injury/etiology ; Reperfusion Injury/pathology ; Reperfusion Injury/therapy ; Tissue Donors
Chemical Substances	Organ Preservation Solutions ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0257783
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Article ; Online: Lessons learned from the COVID-19 pandemic about sample access for research in the UK.

Sims, Jessica M / Lawrence, Emma / Glazer, Katy / Gander, Amir / Fuller, Barry / Davidson, Brian R / Garibaldi, Jonathan / Quinlan, Philip R

BMJ open

2022 Volume 12, Issue 4, Page(s) e047309

Abstract: Objective: Annotated clinical samples taken from patients are a foundation of translational medical research and give mechanistic insight into drug trials. Prior research by the Tissue Directory and Coordination Centre (TDCC) indicated that researchers, ...

Abstract	Objective: Annotated clinical samples taken from patients are a foundation of translational medical research and give mechanistic insight into drug trials. Prior research by the Tissue Directory and Coordination Centre (TDCC) indicated that researchers, particularly those in industry, face many barriers in accessing patient samples. The arrival of the COVID-19 pandemic to the UK produced an immediate and extreme shockwave, which impacted on the ability to undertake all crucial translational research. As a national coordination centre, the TDCC is tasked with improving efficiency in the biobanking sector. Thus, we took responsibility to identify and coordinate UK tissue sample collection organisations (biobanks) able to collect COVID-19-related samples for researchers between March and September 2020. Findings: Almost a third of UK biobanks were closed during the first wave of the UK COVID-19 pandemic. Of the remainder, 43% had limited capabilities while 26% maintained normal activity. Of the nationally prioritised COVID-19 interventional studies, just three of the five that responded to questioning were collecting human samples. Of the 41 requests for COVID-19 samples received by the TDCC, only four could be fulfilled due to a lack of UK coordinated strategy. Meanwhile, in the background there are numerous reports that sample collections in the UK remain largely underutilised. Conclusion: The response to a pandemic demands high level co-ordinated research responses to reduce mortality. Our study highlights the lack of efficiency and coordination between human sample collections and clinical trials across the UK. UK sample access is not working for researchers, clinicians or patients. A radical change is required in the strategy for sample collection and distribution to maximise this valuable resource of human-donated samples.
MeSH term(s)	Biological Specimen Banks ; COVID-19/epidemiology ; Humans ; Pandemics ; United Kingdom/epidemiology
Language	English
Publishing date	2022-04-15
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2020-047309
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Article ; Online: Portal vein embolization versus dual vein embolization for management of the future liver remnant in patients undergoing major hepatectomy: meta-analysis.

Bell, Richard J / Hakeem, Abdul R / Pandanaboyana, Sanjay / Davidson, Brian R / Prasad, Raj K / Dasari, Bobby V M

BJS open

2022 Volume 6, Issue 6

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Humans ; Hepatectomy/methods ; Portal Vein/surgery ; Retrospective Studies ; Liver Neoplasms/surgery ; Hypertrophy/etiology ; Hypertrophy/surgery
Language	English
Publishing date	2022-11-18
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrac131
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