The Leeds Teaching Hospitals NHS Trust


Publications


Uncertain Benefits of Simvastatin in the Treatment of Patients With Variceal Hemorrhage.
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Uncertain Benefits of Simvastatin in the Treatment of Patients With Variceal Hemorrhage.

Gastroenterology. 2016 Oct 3;:

Authors: Chaudhry T, Dillon A, Rowe IA

PMID: 27713045 [PubMed - as supplied by publisher]
Re-appraisal of prophylactic drainage in uncomplicated liver resections: a systematic review and meta-analysis.
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Re-appraisal of prophylactic drainage in uncomplicated liver resections: a systematic review and meta-analysis.

HPB (Oxford). 2016 Aug 26;

Authors: Gavriilidis P, Hidalgo E, de'Angelis N, Lodge P, Azoulay D

Abstract
AIM: The benefit of prophylactic drainage after uncomplicated hepatectomy remains controversial. The aim of this study was to update the existing evidence on the role of prophylactic drainage following uncomplicated liver resection.
METHODS: Cochrane, Medline (Pubmed), and Embase were searched. The Medline search strategy was adopted for all other databases. A grey literature search was performed. Meta-analyses were performed with Review Manager 5.3. Primary outcomes were mortality and ascitic leak, secondary outcomes were infected intra-abdominal collection, chest infection, wound infection of the surgical incision, biliary fistula, and length of stay.
RESULTS: The incidence of ascitic leak was higher in the drained group (Odds Ratio = 3.33 [95% Confidence Interval: 1.66-5.28]). Infected intra-abdominal collections, wound infections, chest infections, biliary fistula, length of stay and mortality were not statistically different between groups.
CONCLUSIONS: The routine utilisation of drains after elective uncomplicated liver resection does not translate into a lower incidence of postoperative complications. Therefore, based on the current available evidence, routine abdominal drainage is not recommended in elective uncomplicated hepatectomy.

PMID: 27576007 [PubMed - as supplied by publisher]
Obesity and colorectal liver metastases: Mechanisms and management.
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Obesity and colorectal liver metastases: Mechanisms and management.

Surg Oncol. 2016 Sep;25(3):246-51

Authors: Pathak S, Pandanaboyana S, Daniels I, Smart N, Prasad KR

Abstract
INTRODUCTION: Colorectal cancer (CRC) is the third commonest malignancy after lung and breast cancer. The most common cause of mortality from CRC is from distant metastases. Obesity is a known risk factor for primary CRC development. However, its role in metastatic disease progression is not fully understood. The article aims to provide an overview of the role of obesity in colorectal liver metastases (CRLM). Furthermore, possible strategies to minimise this effect are discussed. An electronic search of MedLine, EMBASE, CINAHL and google scholar was performed. Relevant articles were included in the article. Obesity causes localised inflammation within the liver microenvironment which may predispose to metastases development. Furthermore, obesity causes systemic inflammation leading to release of protumourigenic growth factors. Several studies demonstrated the effects of lifestyle modification, medications, bariatric surgery and omega-3 fatty acids on steatosis within the context of liver surgery. It is currently unclear whether obesity directly leads to metastatic disease via chronic systemic inflammation or whether obesity induced steatosis provides a fertile microenvironment for metastases deposition. With a global increase in obesity useful strategies to minimise the effects of obesity on the liver include life-style modification, pre-operative dietary regimes and omega-3 fatty acids intake. Pre-operative optimisation of the patient is a key concept. Further randomised control trials are needed to guide management strategies.

PMID: 27566030 [PubMed - in process]
Establishing the independence and clinical importance of non-alcoholic fatty liver disease as a risk factor for cardiovascular disease.
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Establishing the independence and clinical importance of non-alcoholic fatty liver disease as a risk factor for cardiovascular disease.

J Hepatol. 2016 Aug 4;

Authors: Chimakurthi CR, Rowe IA

PMID: 27498134 [PubMed - as supplied by publisher]
Primary liver resection for patients with cirrhosis and hepatocellular carcinoma: the role of surgery in BCLC early (A) and intermediate stages (B).
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Primary liver resection for patients with cirrhosis and hepatocellular carcinoma: the role of surgery in BCLC early (A) and intermediate stages (B).

Langenbecks Arch Surg. 2016 Jul 25;

Authors: Bell R, Pandanaboyana S, Lodge JP, Prasad KR, Jones R, Hidalgo E

Abstract
AIM: This study aims to report the outcomes following primary liver resection (PLR) in patients with cirrhosis including stratification according to the Barcelona Clinic Liver Cancer (BCLC) classification.
METHODS: Patients with cirrhosis and hepatocellular carcinoma (HCC) who had PLR between 2000 and 2013 were examined. Overall survival (OS), disease-free survival (DFS) and recurrence rate (RR) were analysed. Management after recurrence was reviewed as well as comparison to a series of 116 patients listed directly for liver transplant.
RESULTS: Seventy-one patients underwent PLR. Median follow-up was 40 months. The 1-, 3- and 5-year OS and DFS for the series were 77, 69 and 61 % and 69, 39 and 28 % respectively. Overall recurrence was 59 % (44/71) and only 36 % (15/44) of those patients had a further potentially curative procedure. The 1-3-5-year OS and DFS in the BCLC-A (44 patients) were 86, 78 and 68 % and 78, 48 and 44 % respectively. The RR in BCLC-A was 45 % (20 patients) with half (11 patients) suitable for further treatment with curative intent. The 1-3-5-year OS and DFS in the BCLC-B (17 patients) were 81, 74 and 60 % and 58, 29 and 7 % respectively. The overall RR in BCLC-B was 76 % (13 patients).
CONCLUSION: Recurrence following PLR for HCC in patients with cirrhosis is high with only a third of patients suitable for further potentially curative procedures. For patients with BCLC-A (or within Milan criteria), PLR provided a 68 % 5-year OS with 44 % of them free of disease. Surgery can offer satisfactory OS in carefully selected patients in the BCLC-B stage.

PMID: 27456677 [PubMed - as supplied by publisher]
Impact of parenchymal preserving surgery on survival and recurrence after liver resection for colorectal liver metastasis.
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Impact of parenchymal preserving surgery on survival and recurrence after liver resection for colorectal liver metastasis.

ANZ J Surg. 2016 Apr 25;

Authors: Pandanaboyana S, Bell R, White A, Pathak S, Hidalgo E, Lodge P, Prasad R, Toogood G

Abstract
BACKGROUND: This study aimed to investigate the impact of non-anatomical liver resection (NAR) versus anatomical resection (AR) in patients with colorectal liver metastasis (CRLM), with regard to perioperative and long-term outcomes.
METHODS: Analysis of prospectively collected data for patients with CRLM who underwent either AR or NAR between January 1993 and August 2011 was performed. The impact of AR and NAR on morbidity, mortality, margin positivity, redo liver resections, overall survival (OS) and disease free survival (DFS) was analysed.
RESULTS: A total of 1574 resections for CRLM were performed. A total of 249 were redo resections and 334 patients underwent combined AR and NAR, hence, 583 were excluded. In total, 582 AR and 409 NAR were performed. The median age was 66 years (range 23.8-91.8). Median follow up was 32.2 months (interquartile range 17.5-56.9). The need for postoperative transfusion (11.6% versus 2.2%, P = <0.0001), overall complications (25% versus 10.7%, P < 0.0001) and 90-day mortality (4.9% versus 1.2%, P < 0.0001) was higher in the AR group. R0 and R1 resection rates (AR 26.2% NAR 25%, P = 0.69) and number of patients with intrahepatic recurrence was similar between the two groups (AR 17.5% NAR 22%, P = 0.08). However, the need for redo liver surgery was higher in NAR group 15.4% versus 8.7% (P < 0.001). The OS (NAR 34.1 months versus AR 31.4 months, P = 0.002) and DFS were longer in the NAR group (NAR 18.8 months versus AR 16.9 months, P = 0.031).
CONCLUSIONS: A parenchymal preserving surgery (NAR) is associated with lower complication rates and better OS and DFS when compared with AR without compromising margin status. However, NAR increases the need for repeat liver resections.

PMID: 27111217 [PubMed - as supplied by publisher]
Implementation of the Lancet Standing Commission on Liver Disease in the UK.
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Implementation of the Lancet Standing Commission on Liver Disease in the UK.

Lancet. 2015 Nov 21;386(10008):2098-111

Authors: Williams R, Ashton K, Aspinall R, Bellis MA, Bosanquet J, Cramp ME, Day N, Dhawan A, Dillon J, Dyson J, Ferguson J, Foster G, Sir Gilmore I, Glynn M, Guthrie JA, Hudson M, Kelly D, Langford A, Newsome P, O'Grady J, Pryke R, Ryder S, Samyn M, Sheron N, Verne J

PMID: 26700394 [PubMed - indexed for MEDLINE]
Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy.
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Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy.

Br J Surg. 2016 Feb;103(3):249-56

Authors: Farid SG, White A, Khan N, Toogood GJ, Prasad KR, Lodge JP

Abstract
BACKGROUND: Left hepatic trisectionectomy (LHT) is a challenging major anatomical hepatectomy with a high complication rate and a worldwide experience that remains limited. The aim of this study was to describe changes in surgical practice over time, to analyse the outcomes of patients undergoing LHT for hepatobiliary malignancy, and to identify factors associated with morbidity and mortality.
METHODS: A cohort study was undertaken of patients who underwent LHT at a single tertiary hepatobiliary referral centre between January 1993 and March 2013. Univariable and multivariable analysis was used to identify factors associated with short- and long-term outcomes following LHT.
RESULT: Some 113 patients underwent LHT for colorectal liver metastasis (57), hilar cholangiocarcinoma (22), intrahepatic cholangiocarcinoma (12) and hepatocellular carcinoma (11); 11 patients had various other indications. Overall morbidity and 90-day mortality rates were 46.0 and 9.7 per cent respectively. Overall 1- and 3-year survival rates were 71.3 and 44.4 per cent respectively. Total hepatic vascular exclusion and intraoperative blood transfusion were independent predictors of postoperative morbidity, whereas blood transfusion was the only factor predictive of in-hospital mortality. Time period analysis revealed a decreasing trend in blood transfusion, duration of hospital stay, and postoperative morbidity and mortality in the last 5 years.
CONCLUSION: Morbidity, mortality and long-term survival after LHT support its use in selected patients with a significant tumour burden.

PMID: 26695377 [PubMed - indexed for MEDLINE]
Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.
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Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.

Lancet. 2016 Feb 13;387(10019):679-90

Authors: Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, Hazlehurst JM, Guo K, LEAN trial team, Abouda G, Aldersley MA, Stocken D, Gough SC, Tomlinson JW, Brown RM, Hübscher SG, Newsome PN

Abstract
BACKGROUND: Glucagon-like peptide-1 (GLP-1) analogues reduce hepatic steatosis, concentrations of liver enzymes, and insulin resistance in murine models of fatty liver disease. These analogues are licensed for type 2 diabetes, but their efficacy in patients with non-alcoholic steatohepatitis is unknown. We assessed the safety and efficacy of the long-acting GLP-1 analogue, liraglutide, in patients with non-alcoholic steatohepatitis.
METHODS: This multicentre, double-blinded, randomised, placebo-controlled phase 2 trial was conducted in four UK medical centres to assess subcutaneous injections of liraglutide (1·8 mg daily) compared with placebo for patients who are overweight and show clinical evidence of non-alcoholic steatohepatitis. Patients were randomly assigned (1:1) using a computer-generated, centrally administered procedure, stratified by trial centre and diabetes status. The trial was designed using A'Hern's single-group method, which required eight (38%) of 21 successes in the liraglutide group for the effect of liraglutide to be considered clinically significant. Patients, investigators, clinical trial site staff, and pathologists were masked to treatment assignment throughout the study. The primary outcome measure was resolution of definite non-alcoholic steatohepatitis with no worsening in fibrosis from baseline to end of treatment (48 weeks), as assessed centrally by two independent pathologists. Analysis was done by intention-to-treat analysis, which included all patients who underwent end-of-treatment biopsy. The trial was registered with ClinicalTrials.gov, number NCT01237119.
FINDINGS: Between Aug 1, 2010, and May 31, 2013, 26 patients were randomly assigned to receive liraglutide and 26 to placebo. Nine (39%) of 23 patients who received liraglutide and underwent end-of-treatment liver biopsy had resolution of definite non-alcoholic steatohepatitis compared with two (9%) of 22 such patients in the placebo group (relative risk 4·3 [95% CI 1·0-17·7]; p=0·019). Two (9%) of 23 patients in the liraglutide group versus eight (36%) of 22 patients in the placebo group had progression of fibrosis (0·2 [0·1-1·0]; p=0·04). Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, transient, and similar in the two treatment groups for all organ classes and symptoms, with the exception of gastrointestinal disorders in 21 (81%) of 23 patients in the liraglutide group and 17 (65%) of 22 patients in the placebo group, which included diarrhoea (ten [38%] patients in the liraglutide group vs five [19%] in the placebo group), constipation (seven [27%] vs none), and loss of appetite (eight [31%] vs two [8%]).
INTERPRETATION: Liraglutide was safe, well tolerated, and led to histological resolution of non-alcoholic steatohepatitis, warranting extensive, longer-term studies.
FUNDING: Wellcome Trust, National Institute of Health Research, and Novo Nordisk.

PMID: 26608256 [PubMed - indexed for MEDLINE]
Capitalising on improved rates of diagnosis of early hepatocellular carcinoma.
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Capitalising on improved rates of diagnosis of early hepatocellular carcinoma.

J Hepatol. 2016 Feb;64(2):260-1

Authors: Rowe IA, Sherman M

PMID: 26551515 [PubMed - indexed for MEDLINE]
Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis.
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Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis.

Biochim Biophys Acta. 2016 Jan;1862(1):135-44

Authors: Coombes JD, Choi SS, Swiderska-Syn M, Manka P, Reid DT, Palma E, Briones-Orta MA, Xie G, Younis R, Kitamura N, Della Peruta M, Bitencourt S, Dollé L, Oo YH, Mi Z, Kuo PC, Williams R, Chokshi S, Canbay A, Claridge LC, Eksteen B, Diehl AM, Syn WK

Abstract
INTRODUCTION: Liver fibrosis develops when hepatic stellate cells (HSC) are activated into collagen-producing myofibroblasts. In non-alcoholic steatohepatitis (NASH), the adipokine leptin is upregulated, and promotes liver fibrosis by directly activating HSC via the hedgehog pathway. We reported that hedgehog-regulated osteopontin (OPN) plays a key role in promoting liver fibrosis. Herein, we evaluated if OPN mediates leptin-profibrogenic effects in NASH.
METHODS: Leptin-deficient (ob/ob) and wild-type (WT) mice were fed control or methionine-choline deficient (MCD) diet. Liver tissues were assessed by Sirius-red, OPN and αSMA IHC, and qRT-PCR for fibrogenic genes. In vitro, HSC with stable OPN (or control) knockdown were treated with recombinant (r)leptin and OPN-neutralizing or sham-aptamers. HSC response to OPN loss was assessed by wound healing assay. OPN-aptamers were also added to precision-cut liver slices (PCLS), and administered to MCD-fed WT (leptin-intact) mice to determine if OPN neutralization abrogated fibrogenesis.
RESULTS: MCD-fed WT mice developed NASH-fibrosis, upregulated OPN, and accumulated αSMA+ cells. Conversely, MCD-fed ob/ob mice developed less fibrosis and accumulated fewer αSMA+ and OPN+ cells. In vitro, leptin-treated HSC upregulated OPN, αSMA, collagen 1α1 and TGFβ mRNA by nearly 3-fold, but this effect was blunted by OPN loss. Inhibition of PI3K and transduction of dominant negative-Akt abrogated leptin-mediated OPN induction, while constitutive active-Akt upregulated OPN. Finally, OPN neutralization reduced leptin-mediated fibrogenesis in both PCLS and MCD-fed mice.
CONCLUSION: OPN overexpression in NASH enhances leptin-mediated fibrogenesis via PI3K/Akt. OPN neutralization significantly reduces NASH fibrosis, reinforcing the potential utility of targeting OPN in the treatment of patients with advanced NASH.

PMID: 26529285 [PubMed - in process]
Transplantation of liver and kidney from donors with malignancy at the time of donation: an experience from a single centre.
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Transplantation of liver and kidney from donors with malignancy at the time of donation: an experience from a single centre.

Transpl Int. 2016 Jan;29(1):73-80

Authors: Pandanaboyana S, Longbotham D, Hostert L, Attia M, Baker R, Menon K, Ahmad N

Abstract
Transplantation of organs from donors with malignancy poses clinical and ethical questions regarding outcome, informed consent, immunosuppression and follow-up. We review our experience of kidney and liver transplantation from such donors. Our database was complemented by data from National Health Service Blood and Transplant. All patients who received a renal or liver transplant in our institution between April 2003 and January 2014 were included. About 2546 liver and kidney transplants were performed: 71 recipients received 53 kidney and 18 liver transplants. These included 51 (36 kidney, 15 liver) CNS malignancy, and six kidneys, three ipsilateral and three contralateral with RCC. One kidney recipient developed donor-transmitted lung cancer in the transplant kidney, and one liver transplant recipient developed donor-transmitted lymphoma; both subsequently died. Seven recipients developed donor-unrelated cancer. No recipient developed cancer, whereas the donor had a CNS or RCC. The 1-, 3- and 5-year patient survival was 96%, 93.3% and 75%, respectively, for kidneys and 83.3%, 75% and 50%, respectively, for liver. Where donor malignancy was known and assessed before transplantation, judicious use of kidney and liver for transplant achieved satisfactory outcome. The risk of transmission from donors with CNS and low-grade renal malignancy remains extremely low.

PMID: 26402442 [PubMed - indexed for MEDLINE]
Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections.
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Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections.

Int J Surg. 2016 Jan;25:172-7

Authors: Morris-Stiff G, Marangoni G, Hakeem A, Farida SG, Gomez D, Toogood GJ, Lodge JP, Raj Prasad K

Abstract
INTRODUCTION: A major hepatic resection is currently defined as resection of 3 or more segments. The aim of this study was to analyse the post-operative morbidity and mortality of hepatic resections in relation to the number of segments excised.
PATIENTS AND METHODS: From January 2000 to December 2010, 1111 liver resections were performed for colorectal liver metastases (CRLM). Data were collected from a prospectively maintained database and analysed according to the extent of resection performed.
RESULTS: 457 patients had 1-2, 362 had 3-4 and 292 had 5-6 segments resected respectively. In comparing 1-4 vs. 5-6 segments, overall morbidity (16.7% vs 40.7%; p < 0.001), hepatic failure (0.6% vs 10.6%; p < 0.001); mean hospital stay (8 vs 13.5 days; p = 0.000), mean ICU stay (4.4 vs 6.5 days; p = 0.01), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-day mortality (0.7% vs 3.4%; p = 0.002) were significantly different. When analysing the 3-4 vs 5-6 segment resections, morbidity (21.8% vs 40.7%; p < 0.001), hepatic failure (1.4% vs 10.6%; p = 0.000), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-days mortality (0.8% vs 3.4%; p = 0.023) remained statistically significant.
CONCLUSIONS: Differences in outcome would suggest a revision of the current classification. Only when 5 or more segments are excised for CRLM should a liver resection be considered "major".

PMID: 26360739 [PubMed - indexed for MEDLINE]
Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use.
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Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use.

J Hepatol. 2016 Jan;64(1):234-8

Authors: Dyson JK, Hutchinson J, Harrison L, Rotimi O, Tiniakos D, Foster GR, Aldersley MA, McPherson S

Abstract
Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma. There have been rapid advances in HCV treatment with the development of oral direct-acting antivirals (DAAs). Studies have shown sustained virological response rates above 90% with combinations of DAAs, including patients with compensated cirrhosis. Thus far, significant drug toxicity has not been seen with these agents, but there is limited experience of using DAAs in decompensated HCV cirrhosis. This report describes the first experience of serious drug-induced hepatotoxicity with the new DAAs. The mechanism underlying these drug reactions is currently unknown. Few patients with decompensated cirrhosis have been treated with DAAs, so the exact pharmacokinetics in this population have not been characterised. In both cases presented here, patients were taking or had recently taken other drugs. It is possible that an unknown interaction or reaction to the drug combination caused the hepatotoxicity. Although the association with the DAAs is not proven these cases indicate that patients with advanced liver disease need close monitoring while on DAA therapy and if there is a significant unexplained deterioration in liver function the DAAs should be discontinued.

PMID: 26325535 [PubMed - in process]
The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis.
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The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis.

Hepatology. 2016 Mar;63(3):930-50

Authors: Carbone M, Sharp SJ, Flack S, Paximadas D, Spiess K, Adgey C, Griffiths L, Lim R, Trembling P, Williamson K, Wareham NJ, Aldersley M, Bathgate A, Burroughs AK, Heneghan MA, Neuberger JM, Thorburn D, Hirschfield GM, Cordell HJ, Alexander GJ, Jones DE, Sandford RN, Mells GF, UK-PBC Consortium

Abstract
UNLABELLED: The biochemical response to ursodeoxycholic acid (UDCA)--so-called "treatment response"--strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90).
CONCLUSIONS: The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care.

PMID: 26223498 [PubMed - indexed for MEDLINE]
Neonatal organ donation for transplantation in the UK.
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Neonatal organ donation for transplantation in the UK.

Arch Dis Child Fetal Neonatal Ed. 2015 Sep;100(5):F469

Authors: Wijetunga I, Ecuyer C, Martinez-Lopez S, Benetatos N, Griffiths A, Adappa R, Francis C, Murphy P, Ahmad N

PMID: 26126845 [PubMed - indexed for MEDLINE]
Anaesthetic and pharmacological techniques to decrease blood loss in liver surgery: a systematic review.
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Anaesthetic and pharmacological techniques to decrease blood loss in liver surgery: a systematic review.

ANZ J Surg. 2015 Dec;85(12):923-30

Authors: Pathak S, Hakeem A, Pike T, Toogood GJ, Simpson M, Prasad KR, Miskovic D

Abstract
BACKGROUND: There is increasing evidence that perioperative blood loss and blood transfusions are associated with poorer short- and long-term outcomes in patients undergoing hepatectomy. The aim of this study was to systematically review the literature for non-surgical measures to decrease intraoperative blood loss during liver surgery.
METHODS: The literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google Scholar databases. The primary outcome measures were perioperative blood loss and transfusion requirements. A secondary outcome measure was development of ischaemia-reperfusion injury.
RESULTS: Seventeen studies met the inclusion criteria and included 1573 patients. All were randomized controlled studies. In eight studies (n = 894), pharmacological methods, and in another nine studies (n = 679), anaesthetic methods to decrease blood loss were investigated. Anti-fibrinolytic drugs, acute normovolaemic haemodilution, autologous blood donation and use of inhalational anaesthetic agent may affect blood loss and post-operative hepatic function.
CONCLUSIONS: There is potential for use of non-surgical techniques to decrease perioperative bleeding. However, on the basis of this review alone, due to heterogeneity of randomized trials conducted, no particular strategy can be recommended. Future studies should be conducted looking at pathways to decrease bleeding in liver surgery.

PMID: 26074283 [PubMed - in process]
Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.
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Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

PLoS One. 2015;10(5):e0127511

Authors: Tachtatzis PM, Marshall A, Arvinthan A, Aravinthan A, Verma S, Penrhyn-Lowe S, Mela M, Scarpini C, Davies SE, Coleman N, Alexander GJ

Abstract
BACKGROUND: Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.
METHODS: Liver samples from patients with chronic HBV (n = 91), normal liver (n = 55) and regenerating liver (n = 15) were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH) in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro.
RESULTS: 13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9%) in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg) expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect.
CONCLUSION: Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

PMID: 26024529 [PubMed - indexed for MEDLINE]
Survey of the knowledge, perception, and attitude of medical students at the University of Leeds toward organ donation and transplantation.
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Survey of the knowledge, perception, and attitude of medical students at the University of Leeds toward organ donation and transplantation.

Transplant Proc. 2015 Mar;47(2):247-60

Authors: Bedi KK, Hakeem AR, Dave R, Lewington A, Sanfey H, Ahmad N

Abstract
BACKGROUND: The shortage of organ donors is the key rate-limiting factor for organ transplantation in the United Kingdom. Many strategies have been proposed to increase donation; one strategy aims to improve awareness of organ donation and transplantation (ODT) among medical students. This survey seeks to investigate the knowledge, perceptions, and attitudes of the medical students in the United Kingdom toward ODT and the curriculum content.
METHODS: A 32-item online questionnaire was distributed to 957 medical students at the University of Leeds (October to December 2012).
RESULTS: There were 216 (22.6%) respondents. Students were aware of kidney, heart, and liver transplantation (91.6%, 88.8%, and 86.5%). Awareness of small intestine (36.7%) and islet of Langerhans (33.0%) transplantation was poor. Students understood the term "brain stem death" (82.3%); however, they lacked understanding of criteria used for brain stem death testing (75.8%). Their perceptions and attitudes were favorable toward ODT; 43.3% of the students were unhappy with their current knowledge, and 87.6% of the students agree that ODT teaching should be included in the curriculum.
CONCLUSIONS: Students have a basic understanding of ODT but lack detailed knowledge. They accept its importance and desire further teaching to supplement their current knowledge to be able to understand the issues related to ODT.

PMID: 25769557 [PubMed - indexed for MEDLINE]
A systematic review and meta-analysis of portal vein ligation versus portal vein embolization for elective liver resection.
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A systematic review and meta-analysis of portal vein ligation versus portal vein embolization for elective liver resection.

Surgery. 2015 Apr;157(4):690-8

Authors: Pandanaboyana S, Bell R, Hidalgo E, Toogood G, Prasad KR, Bartlett A, Lodge JP

Abstract
INTRODUCTION: This meta-analysis aimed to review the percentage increase in future liver remnant (FLR) and perioperative outcomes after portal vein ligation (PVL) and portal vein embolization (PVE) before liver resection.
METHODS: An electronic search was performed of the MEDLINE, EMBASE, and PubMed databases using both subject headings (MeSH) and truncated word searches to identify all articles published that related to this topic. Pooled risk ratios were calculated for categorical outcomes and mean differences for secondary continuous outcomes using the fixed-effects and random-effects models for meta-analysis.
RESULTS: Seven studies involving 218 patients met the inclusion criteria. There was no difference in the increase in FLR between the 2 groups 39% (PVE) versus 27% (PVL; mean difference [MD] 6.04; 95% CI, -0.23, 12.32; Z = 1.89; P = .06). Similarly, there was no difference in the morbidity (risk ratio [RR], 1.08; 95% CI, 0.55, 2.09; Z = 0.21; P = .83) and mortality (RR, 0.87; 95% CI, 0.19, 3.92; Z = 0.18; P = .85) in the 2 groups after liver resection. While awaiting liver resection after PVL and PVE, no difference was noted in the number of patients developing disease progression (RR, 0.93; 95% CI, 0.52, 1.66; Z = 0.24; P = .81). In a subset analysis comparing FLR with PVE and PVL as part of the procedure called an associating liver partition with PVL for staged hepatectomy (ALPPS), there was a significant increase in FLR in favor of ALPPS (MD, -17.09; 95% CI, -32.78, -1.40; Z = 2.14; P = .03).
CONCLUSION: PVL and PVE result in comparable percentage increase in FLR with similar morbidity and mortality rates. The ALPPS procedure results in an improved percentage increase in FLR compared with PVE alone.

PMID: 25704417 [PubMed - indexed for MEDLINE]
A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases.
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A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases.

ANZ J Surg. 2014 Dec 30;

Authors: Pandanaboyana S, Bell R, Shah N, Lodge JP, Hidalgo E, Toogood GJ, Prasad KR

Abstract
BACKGROUND: There is paucity of data regarding the cost-effectiveness of fibrin sealants during liver surgery. This study aimed to assess the cost-effectiveness of fibrin sealants following right hemihepatectomy for colorectal liver metastases.
METHOD: A prospectively maintained database between 2004 and 2013 was reviewed to identify patients who underwent a right hemihepatectomy with and without fibrin sealant application. Perioperative and post-operative outcomes were analysed to assess its cost-effectiveness.
RESULTS: One hundred and sixty-three right hemihepatectomies were performed, of which 79 were in the fibrin sealant treatment group and 84 were in the no sealant group. No difference was seen between fibrin sealant and no sealant with regard to bile leak (P = 0.366), intra-abdominal collections (P = 0.200) and overall post-operative complications (P = 0.480). Operating costs were significantly cheaper in the no sealant group (P = 0.010). There was no difference seen in median post-operative stay between fibrin sealant versus no treatment (8 versus 9 days, P = 0.327), median total bed cost (£3900 versus £4300, P = 0.400), mean transfusion cost per patient (P = 0.201) and overall cost (£6706.15 versus £6555.80, P = 0.792).
CONCLUSION: Fibrin sealant application to cut surface during liver surgery confers no cost benefit and their routine use may not be recommended.

PMID: 25641546 [PubMed - as supplied by publisher]
Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.
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Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.

Br J Surg. 2015 Mar;102(4):388-98

Authors: Roberts KJ, Sutton AJ, Prasad KR, Toogood GJ, Lodge JP

Abstract
BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy).
METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting.
RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (€22,200 versus €32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario.
CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.

PMID: 25624168 [PubMed - indexed for MEDLINE]
Meta-analysis of Duct-to-duct versus Roux-en-Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis.
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Meta-analysis of Duct-to-duct versus Roux-en-Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis.

Transpl Int. 2015 Apr;28(4):485-91

Authors: Pandanaboyana S, Bell R, Bartlett AJ, McCall J, Hidalgo E

Abstract
This meta-analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct-to-duct or Roux-en-Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed-effects and random-effects models for meta-analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux-en-Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct-to-duct and Roux-en-Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct-to-duct reconstruction should be considered when feasible in patients with PSC.

PMID: 25557556 [PubMed - indexed for MEDLINE]
Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.
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Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.

Br J Surg. 2015 Feb;102(3):261-8

Authors: Dave RV, Pathak S, White AD, Hidalgo E, Prasad KR, Lodge JP, Milton R, Toogood GJ

Abstract
BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC.
METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment.
RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit.
CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.

PMID: 25529247 [PubMed - indexed for MEDLINE]
Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.
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Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.

Clin Exp Immunol. 2015 Apr;180(1):98-107

Authors: El-Sherbiny YM, Holmes TD, Wetherill LF, Black EV, Wilson EB, Phillips SL, Scott GB, Adair RA, Dave R, Scott KJ, Morgan RS, Coffey M, Toogood GJ, Melcher AA, Cook GP

Abstract
Human natural killer (NK) cells play an important role in anti-viral immunity. However, studying their activation kinetics during infection is highly problematic. A clinical trial of a therapeutic virus provided an opportunity to study human NK cell activation in vivo in a controlled manner. Ten colorectal cancer patients with liver metastases received between one and five doses of oncolytic reovirus prior to surgical resection of their tumour. NK cell surface expression of the interferon-inducible molecules CD69 and tetherin peaked 24-48 h post-infection, coincident with a peak of interferon-induced gene expression. The interferon response and NK cell activation were transient, declining by 96 h post-infection. Furthermore, neither NK cell activation nor the interferon response were sustained in patients undergoing multiple rounds of virus treatment. These results show that reovirus modulates human NK cell activity in vivo and suggest that this may contribute to any therapeutic effect of this oncolytic virus. Detection of a single, transient peak of activation, despite multiple treatment rounds, has implications for the design of reovirus-based therapy. Furthermore, our results suggest the existence of a post-infection refractory period when the interferon response and NK cell activation are blunted. This refractory period has been observed previously in animal models and may underlie the enhanced susceptibility to secondary infections that is seen following viral infection.

PMID: 25469725 [PubMed - indexed for MEDLINE]
A cost effective analysis of a laparoscopic versus an open left lateral sectionectomy in a liver transplant unit.
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A cost effective analysis of a laparoscopic versus an open left lateral sectionectomy in a liver transplant unit.

HPB (Oxford). 2015 Apr;17(4):332-6

Authors: Bell R, Pandanaboyana S, Hanif F, Shah N, Hidalgo E, Lodge JP, Toogood G, Prasad KR

Abstract
INTRODUCTION: This study aimed to assess the cost effectiveness of a laparoscopic left lateral sectionectomy (LLLS) compared with an open (OLLS) procedure and its role as a training operation as well as the learning curve associated with a laparoscopic approach.
METHOD: Between 2004 and 2013, a prospectively maintained database was reviewed. LLLS were compared with age- and sex-matched OLLS. In addition, the outcomes of LLLS with a consultant as the primary surgeon were compared with those performed by trainees.
RESULTS: Forty-three LLLS were performed during the study period. LLLS was a significantly cheaper operation compared with OLLS (P = 0.001, £3594.14 versus £5593.41). The median hospital stay was shorter in the laparoscopic group (P = 0.002, 3 versus 7 days). No difference was found in outcomes between a LLLS performed by a trainee or consultant (operating time, morbidity or R1 resection rate). The procedure length was significantly shorter during the later half of the study period [120 versus 129 min (P = 0.045)].
CONCLUSION: LLLS is a significantly cost effective operation compared with an open approach with a reduction in hospital stay. In addition, it is suitable to use as a training operation.

PMID: 25403492 [PubMed - indexed for MEDLINE]
Hepatocellular carcinoma in variegate porphyria: a case report and literature review.
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Hepatocellular carcinoma in variegate porphyria: a case report and literature review.

Ann Clin Biochem. 2015 May;52(Pt 3):407-12

Authors: Luvai A, Mbagaya W, Narayanan D, Degg T, Toogood G, Wyatt JI, Swinson D, Hall CJ, Barth JH

Abstract
Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication.

PMID: 25301776 [PubMed - indexed for MEDLINE]
The management of the surgical complications of HELLP syndrome.
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The management of the surgical complications of HELLP syndrome.

Ann R Coll Surg Engl. 2014 Oct;96(7):512-6

Authors: Wilson SG, White AD, Young AL, Davies MH, Pollard SG

Abstract
INTRODUCTION: Complications from HELLP (Haemolysis, Elevated Liver enzymes and Low Platelet) syndrome may present as an emergency to any surgeon. We review the ten-year experience of a tertiary hepatobiliary centre managing HELLP patients. Three selected cases are described to highlight our management strategy and a systematic review of the recent literature is presented.
METHODS: All patients with HELLP syndrome were identified from a prospectively maintained database and their details collated. Subsequently, a detailed search of PubMed was carried out to identify all case series of HELLP syndrome in the literature in the English language since 1999.
RESULTS: On review of 1,002 cases, 10 patients were identified with surgical complications of HELLP syndrome. Seven of these patients had a significant liver injury. Only three of these required surgical intervention for liver injury although four other patients required surgical intervention for other complications. There was no maternal mortality in this series. Review of the literature identified 49 cases in 31 publications. The management approaches of these patients were compared with ours.
CONCLUSIONS: We have presented a large series of patients with surgical complications resulting from HELLP syndrome managed without maternal mortality. This review has confirmed that haemodynamically stable patients with HELLP syndrome associated hepatic rupture can be conservatively treated successfully. However, in unstable patients, perihepatic packing and transfer to a specialist liver unit is recommended.

PMID: 25245729 [PubMed - indexed for MEDLINE]
Does the extent of lymphadenectomy, number of lymph nodes, positive lymph node ratio and neutrophil-lymphocyte ratio impact surgical outcome of perihilar cholangiocarcinoma?
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Does the extent of lymphadenectomy, number of lymph nodes, positive lymph node ratio and neutrophil-lymphocyte ratio impact surgical outcome of perihilar cholangiocarcinoma?

Eur J Gastroenterol Hepatol. 2014 Sep;26(9):1047-54

Authors: Hakeem AR, Marangoni G, Chapman SJ, Young RS, Nair A, Hidalgo EL, Toogood GJ, Wyatt JI, Lodge PA, Prasad KR

Abstract
BACKGROUND: Lymph node (LN) status is an important predictor of survival following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still exist with regard to the prognostic value of optimum extent of lymphadenectomy, total number of nodes removed, LN ratio (LNR) and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA resection.
METHODS: From 1994 to 2010, 84 PHCCAs were resected; 78 are included in this analysis. Kaplan-Meier survival curves were studied using log-rank statistics to assess which variables affected OS and DFS. The variables that showed statistical significance (P<0.05) on Kaplan-Meier univariate analysis were subjected to multivariate analysis using Cox proportional hazards model.
RESULTS: Five-year OS for node-positive status (n=45) was 10%, whereas node-negative (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive group (8%) than in the node-negative group (36%, P=0.001). There was no difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518) between those with regional lymphadenectomy and those who underwent regional plus para-aortic lymphadenectomy, respectively. On univariate analysis, patients with 20 or more LNs removed had worse 5-year OS (0%) when compared with those with less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation, distant metastasis and LN involvement were independent predictors of OS. Positive LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were independent predictors of DFS. NLR had no effect on OS and DFS.
CONCLUSION: Extended lymphadenectomy patients (≥20 LNs) had worse OS when compared with those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an independent predictor of DFS.

PMID: 25051217 [PubMed - indexed for MEDLINE]
Relationship between primary colorectal tumour and location of colorectal liver metastases.
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Relationship between primary colorectal tumour and location of colorectal liver metastases.

ANZ J Surg. 2016 May;86(5):408-10

Authors: Pathak S, Palkhi E, Dave R, White A, Pandanaboyana S, Prasad KR, Lodge JP, Toogood GJ

Abstract
BACKGROUND: There is conflicting evidence regarding whether streamlining of blood flow within the portal vein influences the anatomical distribution of colorectal liver metastases (CRLM). This study assesses the relationship between primary tumour location and metastases location.
METHODS: Patients were identified using a prospectively maintained database, and those with known site of primary colorectal tumour and hemiliver involvement were included. Site of metastases and segments affected were confirmed via review of the radiology reports. The location of primary colonic tumour was confirmed via review of clinical correspondence letters.
RESULTS: A total of 2364 metastases were identified in 891 patients. Of these, 379 metastases were in the right lobe and 156 in the left lobe, with 356 having bilobar disease. There was no significant relationship between the distribution of CRLM and the site of primary disease (left colon versus right colon) (P = 0.819). However, when the segmental location of the metastases was considered, there is a statistically significant difference between the number of right-sided CRLM compared with left-sided CRLM (P < 0.001).
CONCLUSIONS: Right-sided CRLM is more likely regardless of the primary location. Portal streaming may have an effect, although the natural anatomical 'angulation', particularly of the left portal vein branch is more likely to play a role.

PMID: 25040656 [PubMed - in process]
Portal vein arterialization: 'enjoy' it responsibly.
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Portal vein arterialization: 'enjoy' it responsibly.

HPB (Oxford). 2014 Aug;16(8):739

Authors: Hidalgo E

PMID: 25040489 [PubMed - indexed for MEDLINE]
Epidural versus local anaesthetic infiltration via wound catheters in open liver resection: a meta-analysis.
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Epidural versus local anaesthetic infiltration via wound catheters in open liver resection: a meta-analysis.

ANZ J Surg. 2015 Jan;85(1-2):16-21

Authors: Bell R, Pandanaboyana S, Prasad KR

Abstract
BACKGROUND: This meta-analysis was designed to systematically analyse all published studies comparing local anaesthetic infiltration with wound catheters and epidural catheters in open liver resection.
METHODS: A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials, and prospective and retrospective studies comparing wound catheters with epidural catheters were included. Statistical analysis was performed using Review Manager Version 5.2 software. The primary outcome measures were pain scores in the post-operative period operation. Secondary outcome measures were hospital stay, time to opening bowels, overall complications and analgesia-specific complications.
RESULTS: Four studies including 705 patients were included in the analysis. The pain scores were significantly lower in those patients with epidural on the first post-operative day (POD) (mean difference of -0.90 [-1.29, -0.52], Z = 4.61) (P < 0.00001) with comparable pain scores on PODs 2 and 3. There was no significant difference in the time to opening bowels, opioid use and hospital stay between the techniques. The post-operative complication rate was higher in the epidural group (risk ratio 1.40 [1.07, 1.83]; χ(2) = 0.60, df = 1) (P = 0.44); I(2) = 0%; Z = 2.42 (P = 0.02).
CONCLUSION: Local anaesthetic infiltration via wound catheters combined with patient-controlled opiate analgesia provides comparable pain relief to epidural catheters except for the first POD. Both techniques are associated with similar hospital stay and opioid use with wound catheters associated with lower complication rate.

PMID: 24888251 [PubMed - indexed for MEDLINE]
Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome.
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Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome.

Case Rep Transplant. 2014;2014:272498

Authors: Craig DG, Lee P, Pryde EA, Hidalgo E, Hayes PC, Wigmore SJ, Forbes SJ, Simpson KJ

Abstract
Background. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE) to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE. Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS. Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF) and 6 healthy controls (HC). Results. HMGB1 levels were markedly higher in the SFSS patient (92.1 ng/mL) compared with the ALF patients (median (IQR) 11.4 (3.7-14.8) ng/mL) and HC (1.42 (1.38-1.56) ng/mL). In contrast, sRAGE levels were lower in the SFSS patient (1.88 ng/mL) compared with the ALF patients (3.53 (2.66-12.37) ng/mL) and were similar to HC levels (1.40 (1.23-1.89) ng/mL). Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition.

PMID: 24600525 [PubMed]
Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid.
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Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid.

Gut. 2014 Nov;63(11):1760-8

Authors: Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, Loadman PM, Toogood GJ, Hull MA

Abstract
BACKGROUND: Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM).
DESIGN: We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2 g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS).
RESULTS: The median (range) duration of EPA-FFA treatment was 30 (12-65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in 'EPA-naïve' individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18 months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar.
CONCLUSIONS: EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted.
TRIAL IDENTIFIER: ClinicalTrials.gov NCT01070355.

PMID: 24470281 [PubMed - indexed for MEDLINE]
Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.
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Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.

Clin Sci (Lond). 2014 Jun;126(12):845-55

Authors: Choi SS, Claridge LC, Jhaveri R, Swiderska-Syn M, Clark P, Suzuki A, Pereira TA, Mi Z, Kuo PC, Guy CD, Pereira FE, Diehl AM, Patel K, Syn WK

Abstract
OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected cells. Hence we hypothesized that OPN directly promotes HCV replication, and that targeting OPN could be beneficial in HCV. In the present study, we compared the expression of OPN mRNA and protein in HCV (JFH1)-infected Huh7 and Huh7.5 cells, and evaluated whether modulating OPN levels using exogenous OPN ligands (up-regulate OPN) or OPN-specific RNA-aptamers (neutralize OPN) leads to changes in HCV expression. Sera and livers from patients with chronic HCV were analysed to determine whether OPN levels were associated with disease severity or response to therapy. Compared with Huh7 cells, Huh7.5 cells support higher levels of HCV replication (15-fold) and expressed significantly more OPN mRNA (30-fold) and protein. Treating Huh7 cells with OPN ligands led to a dose-related increase in HCV (15-fold) and OPN (8-fold) mRNA. Conversely, treating Huh7.5 cells with OPN-specific RNA aptamers inhibited HCV RNA and protein by >50% and repressed OPN mRNA to basal levels. Liver OPN expression was significantly higher (3-fold) in patients with advanced fibrosis. Serum OPN positively correlated with fibrosis-stage (P=0.009), but negatively correlated with ETBCR (end-of-treatment biochemical response), ETVR (end-of-treatment virological response), SBCR (sustained biochemical response) and SVR (sustained virological response) (P=0.007). The OPN fibrosis score (serum OPN and presence of fibrosis ≥F2) may be a predictor of SVR. In conclusion, OPN is up-regulated in the liver and serum of patients with chronic hepatitis C, and supports increased viral replication. OPN neutralization may be a novel therapeutic strategy in chronic hepatitis C.

PMID: 24438228 [PubMed - indexed for MEDLINE]
Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.
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Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.

Eur J Surg Oncol. 2014 Aug;40(8):1016-20

Authors: Morris-Stiff G, White AD, Gomez D, Cameron IC, Farid S, Toogood GJ, Lodge JP, Prasad KR

Abstract
INTRODUCTION: Sinusoidal obstructive syndrome (SOS) is well associated with the use oxaliplatin-based chemotherapy, and represents a spectrum of hepatotoxicity, with nodular regenerative hyperplasia (NRH) representing the most significant degree of injury. The aim of this study was to determine the prevalence of NRH in patients undergoing resection of colorectal liver metastases (CRLM) and to determine its impact on outcome.
METHODS: From January 2000 to December 2010, some 978 first primary liver resections were performed for CRLM. A prospectively maintained database was analysed to identify all patients with evidence of NRH in the non-tumour portion of their histopathology specimens. Clinical data of these patients was reviewed and outcomes assessed.
RESULTS: Five patients exhibited NRH (four males, one female) with a median age of 69 years (range: 35-74). Three patients presented with synchronous hepatic metastases, and two with metachronous lesions. All received at least 6 cycles of oxaliplatin as either adjuvant or neo-adjuvant chemotherapy. Only one patient developed a post-operative complication namely transient hepatic failure that required a 4-day stay in the intensive care unit. The median hospital stay was 6 days (range: 6-14 days). There were no 90-day mortalities. One patient is alive and disease free at 55 months, the remaining 4 died of recurrent disease between 37 and 70 months following diagnosis of their primary tumours.
CONCLUSIONS: NRH is not an uncommon finding amongst patients with SOS with all patients having received oxaliplatin-based chemotherapy. Data on outcome would suggest no increased morbidity and mortality associated with the presence of NRH.

PMID: 24370284 [PubMed - indexed for MEDLINE]
Is liver transplant for alcohol-related end-stage liver disease appropriate?
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Is liver transplant for alcohol-related end-stage liver disease appropriate?

Br J Hosp Med (Lond). 2013 Aug;74(8):439-42

Authors: Bailey D, Pathak S, Ahmad N

PMID: 23958981 [PubMed - indexed for MEDLINE]
Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure.
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Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure.

HPB (Oxford). 2014 Mar;16(3):220-8

Authors: Rajput I, Prasad KR, Bellamy MC, Davies M, Attia MS, Lodge JP

Abstract
BACKGROUND: An acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively.
RESULTS: During 1998-2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036).
CONCLUSION: Although OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.

PMID: 23870048 [PubMed - indexed for MEDLINE]
Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.
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Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.

HPB (Oxford). 2014 Mar;16(3):212-9

Authors: Ziff O, Rajput I, Adair R, Toogood GJ, Prasad KR, Lodge JP

Abstract
OBJECTIVE: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM).
METHODS: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival.
RESULTS: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified.
CONCLUSION: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.

PMID: 23870012 [PubMed - indexed for MEDLINE]
One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.
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One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.

Ann Surg. 2014 Mar;259(3):543-8

Authors: Hamady ZZ, Lodge JP, Welsh FK, Toogood GJ, White A, John T, Rees M

Abstract
OBJECTIVE: To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases.
BACKGROUND: There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing.
METHODS: Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias.
RESULTS: A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062).
CONCLUSION: One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.

PMID: 23732261 [PubMed - indexed for MEDLINE]
Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation?
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Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation?

HPB (Oxford). 2013 Jun;15(6):418-27

Authors: Young RS, Aldiwani M, Hakeem AR, Nair A, Guthrie A, Wyatt J, Treanor D, Morris-Stiff G, Jones RL, Prasad KR

Abstract
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.

PMID: 23458127 [PubMed - indexed for MEDLINE]
Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases.
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Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases.

BMC Cancer. 2013;13:92

Authors: Young AL, Chalmers CR, Hawcroft G, Perry SL, Treanor D, Toogood GJ, Jones PF, Hull MA

Abstract
BACKGROUND: Prostaglandin (PG) E2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE2 content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE2 in human CRC cells in vitro.
METHODS: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE2 levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β.
RESULTS: PGE2 levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE2. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.
CONCLUSIONS: There is significant intra-tumoral heterogeneity in PGE2 content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE2 metabolism should be targeted for novel treatment of advanced CRC.

PMID: 23442768 [PubMed - indexed for MEDLINE]
Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom.
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Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom.

Liver Transpl. 2013 May;19(5):551-62

Authors: Hakeem AR, Cockbain AJ, Raza SS, Pollard SG, Toogood GJ, Attia MA, Ahmad N, Hidalgo EL, Prasad KR, Menon KV

Abstract
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.

PMID: 23408499 [PubMed - indexed for MEDLINE]
Cytotoxic and immune-mediated killing of human colorectal cancer by reovirus-loaded blood and liver mononuclear cells.
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Cytotoxic and immune-mediated killing of human colorectal cancer by reovirus-loaded blood and liver mononuclear cells.

Int J Cancer. 2013 May 15;132(10):2327-38

Authors: Adair RA, Scott KJ, Fraser S, Errington-Mais F, Pandha H, Coffey M, Selby P, Cook GP, Vile R, Harrington KJ, Toogood G, Melcher AA

Abstract
Reovirus is a promising oncolytic virus, acting by both direct and immune-mediated mechanisms, although its potential may be limited by inactivation after systemic delivery. Our study addressed whether systemically delivered reovirus might be shielded from neutralising antibodies by cell carriage and whether virus-loaded blood or hepatic innate immune effector cells become activated to kill colorectal cancer cells metastatic to the liver in human systems. We found that reovirus was directly cytotoxic against tumour cells but not against fresh hepatocytes. Although direct tumour cell killing by neat virus was significantly reduced in the presence of neutralising serum, reovirus was protected when loaded onto peripheral blood mononuclear cells, which may carry virus after intravenous administration in patients. As well as handing off virus for direct oncolytic killing, natural killer (NK) cells within reovirus-treated blood mononuclear cells were stimulated to kill tumour targets, but not normal hepatocytes, in a Type I interferon-dependent manner. Similarly, NK cells within liver mononuclear cells became selectively cytotoxic towards tumour cells when activated by reovirus. Hence, intravenous reovirus may evade neutralisation by serum via binding to circulating mononuclear cells, and this blood cell carriage has the potential to investigate both direct and innate immune-mediated therapy against human colorectal or other cancers metastatic to the liver.

PMID: 23114986 [PubMed - indexed for MEDLINE]
Repeat hepatic resection for colorectal liver metastases.
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Repeat hepatic resection for colorectal liver metastases.

Br J Surg. 2012 Sep;99(9):1278-83

Authors: Adair RA, Young AL, Cockbain AJ, Malde D, Prasad KR, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Some 75-80 per cent of patients undergoing liver resection for colorectal liver metastases develop intrahepatic recurrence. A significant number of these can be considered for repeat liver surgery. This study examined the outcomes of repeat liver resection for the treatment of recurrent colorectal metastases confined to the liver.
METHODS: Patients who underwent repeat liver resection in a single tertiary referral hepatobiliary centre were identified from a database. Clinicopathological variables were analysed to assess factors predictive of survival.
RESULTS: A total of 195 patients underwent repeat resection between 1993 and 2010. Median age was 63 years, and the median interval between first and repeat resection was 13·8 months. Thirty-three patients (16·9 per cent) underwent completion hemihepatectomy or extended hemihepatectomy and the remainder had non-anatomical or segmental resection. The 30-day mortality rate was 1·5 per cent, and the overall 30-day morbidity rate was 20·0 per cent. Overall 1-, 3- and 5-year survival rates were 91·2, 44·3 and 29·4 per cent respectively. Tumour size 5 cm or greater was the only independent predictor of overall survival (relative risk 1·71, 95 per cent confidence interval 1·08 to 2·70; P = 0·021). Neoadjuvant chemotherapy before resection, perioperative blood transfusion, bilobar disease, R1 resection margin and multiple metastases were among factors that did not significantly influence survival.
CONCLUSION: Repeat hepatic resection remains the only curative option for patients presenting with recurrent colorectal liver metastases.

PMID: 22864889 [PubMed - indexed for MEDLINE]
Cell carriage, delivery, and selective replication of an oncolytic virus in tumor in patients.
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Cell carriage, delivery, and selective replication of an oncolytic virus in tumor in patients.

Sci Transl Med. 2012 Jun 13;4(138):138ra77

Authors: Adair RA, Roulstone V, Scott KJ, Morgan R, Nuovo GJ, Fuller M, Beirne D, West EJ, Jennings VA, Rose A, Kyula J, Fraser S, Dave R, Anthoney DA, Merrick A, Prestwich R, Aldouri A, Donnelly O, Pandha H, Coffey M, Selby P, Vile R, Toogood G, Harrington K, Melcher AA

Abstract
Oncolytic viruses, which preferentially lyse cancer cells and stimulate an antitumor immune response, represent a promising approach to the treatment of cancer. However, how they evade the antiviral immune response and their selective delivery to, and replication in, tumor over normal tissue has not been investigated in humans. Here, we treated patients with a single cycle of intravenous reovirus before planned surgery to resect colorectal cancer metastases in the liver. Tracking the viral genome in the circulation showed that reovirus could be detected in plasma and blood mononuclear, granulocyte, and platelet cell compartments after infusion. Despite the presence of neutralizing antibodies before viral infusion in all patients, replication-competent reovirus that retained cytotoxicity was recovered from blood cells but not plasma, suggesting that transport by cells could protect virus for potential delivery to tumors. Analysis of surgical specimens demonstrated greater, preferential expression of reovirus protein in malignant cells compared to either tumor stroma or surrounding normal liver tissue. There was evidence of viral factories within tumor, and recovery of replicating virus from tumor (but not normal liver) was achieved in all four patients from whom fresh tissue was available. Hence, reovirus could be protected from neutralizing antibodies after systemic administration by immune cell carriage, which delivered reovirus to tumor. These findings suggest new preclinical and clinical scheduling and treatment combination strategies to enhance in vivo immune evasion and effective intravenous delivery of oncolytic viruses to patients in vivo.

PMID: 22700953 [PubMed - indexed for MEDLINE]
An in vitro model of warm hypoxia-reoxygenation injury in human liver endothelial cells.
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An in vitro model of warm hypoxia-reoxygenation injury in human liver endothelial cells.

J Surg Res. 2012 Nov;178(1):e35-41

Authors: Banga NR, Prasad KR, Burn JL, Homer-Vanniasinkam S, Graham A

Abstract
BACKGROUND: Ischemia-reperfusion or hypoxia-reoxygenation (H-R) injury adversely affects hepatic function following transplantation and major resection; the death of human sinusoidal endothelial cells (SECs) by apoptosis may play a central role in this process. Caspase-3 is an important intracellular protease in the intrinsic and extrinsic pathways of apoptosis.
MATERIALS AND METHODS: SECs and EAhy926 cells were exposed to warm hypoxia at 37°C, followed by reoxygenation at 37°C. Activity of caspase-3 was quantified using Western blotting and colorimetric kinase assays.
RESULTS: H-R caused a significant increase in caspase-3 activity compared with controls in both cell types.
CONCLUSIONS: Warm H-R injury causes apoptotic cell death of SECs and immortalized cells, but with differing patterns of caspase activity.

PMID: 22472696 [PubMed - indexed for MEDLINE]
Systematic review: the prognostic role of alpha-fetoprotein following liver transplantation for hepatocellular carcinoma.
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Systematic review: the prognostic role of alpha-fetoprotein following liver transplantation for hepatocellular carcinoma.

Aliment Pharmacol Ther. 2012 May;35(9):987-99

Authors: Hakeem AR, Young RS, Marangoni G, Lodge JP, Prasad KR

Abstract
BACKGROUND: Liver transplantation (LT) offers a possible cure for carefully selected patients with hepatocellular carcinoma (HCC). Studies report that preoperative alpha-fetoprotein (AFP) is a prognostic indicator that can predict survival and recurrence in these patients.
AIM: To undertake a systematic review of available literature on preoperative AFP as a predictor of survival and recurrence following LT for HCC.
METHODS: A literature search was performed using Medline, Embase, Cochrane Library, CINAHL and Google scholar databases to identify studies reporting AFP as a prognostic marker in LT for HCC. Primary outcomes of interest were overall survival and recurrence. Secondary outcomes were correlation of pre-LT AFP with vascular invasion and grade of tumour differentiation.
RESULTS: A total of 13 studies met the inclusion criteria (12,159 patients). The majority were male (9603, 78.9%). All were observational studies and only one prospective. Methodological quality was rated as poor for all studies, with selection and observer bias apparent for most cohorts. Reported survival rates and recurrence rates varied widely between the studies although overall demonstrated better outcomes for those with lower (<1000 ng/mL) pre-LT AFP levels. Similarly, rates of vascular invasion and poor tumour differentiation were higher in those with high pre-LT AFP levels.
CONCLUSIONS: A quantity of AFP >1000 ng/mL is associated with poorer outcomes from liver transplantation for hepatocellular carcinoma. The quality of studies was generally poor and precluded valid statistical meta-analysis. There is a need to improve the performance and reporting of primary prognostic studies to facilitate high quality systematic review and meta-analysis.

PMID: 22429190 [PubMed - indexed for MEDLINE]
Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons.
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Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons.

Colorectal Dis. 2012 Aug;14(8):e477-85

Authors: Qureshi MS, Goldsmith PJ, Maslekar S, Prasad KR, Botterill ID

Abstract
AIM: The optimal management of patients presenting with colorectal cancer and synchronous liver metastases is controversial. This survey was intended to summarize the opinions of UK colorectal and liver surgeons on the specific issues pertaining to synchronous resection.
METHOD: A validated electronic survey was sent to the consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of Upper Gastrointestinal Surgeons (AUGIS). The questions were structured to allow direct comparison between the two groups of the responses obtained.
RESULTS: Four hundred and twenty-four specialist colorectal surgeons and 52 specialist hepatobiliary surgeons were identified from the register of their respective associations. Responses were obtained from 133 (31%) colorectal and 22 (42%) liver surgeons. A majority of both groups of surgeons felt that synchronous resection was a valid therapeutic option. A majority of both groups believed that synchronous resection was justified despite the options of laparoscopic surgery and enhanced recovery programmes for each discipline. Agreed possible advantages of synchronous resections were: a decrease in the overall length of hospital stay, cost and patient anxiety. The major concern about synchronous resections was an excessive overall physiological insult. Specific scenarios indicated that synchronous resection was favoured for major/complex major colorectal resection with minor liver resection or most colorectal resections not involving an anastomosis with either a minor or major liver resection.
CONCLUSION: Although significant concerns relating to synchronous resection remain amongst colorectal and liver surgeons, a majority of them felt that synchronous resections could be offered to appropriately selected patients.

PMID: 22340783 [PubMed - indexed for MEDLINE]
Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study.
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Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study.

HPB (Oxford). 2012 Mar;14(3):194-200

Authors: Young AL, Wilson D, Ward J, Biglands J, Guthrie JA, Prasad KR, Toogood GJ, Robinson PJ, Lodge JP

Abstract
OBJECTIVES: Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis.
METHODS: Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed.
RESULTS: In 10 of the 30 patients the planned liver resection was altered. Moderate-severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2-17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5-17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001).
CONCLUSIONS: This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy.

PMID: 22321038 [PubMed - indexed for MEDLINE]
Biliary papillomatosis in three Caucasian patients in a Western centre.
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Biliary papillomatosis in three Caucasian patients in a Western centre.

Eur J Surg Oncol. 2012 Feb;38(2):181-4

Authors: White AD, Young AL, Verbeke C, Brannan R, Smith A, Prasad KR

Abstract
INTRODUCTION: Biliary papillomatosis (BP) is a rare condition with a strong potential for malignant transformation and cases from Western centres are sparse.(1) We discuss the presentation, investigation and management of this condition in three Caucasian patients and present a review of the existing literature on BP.
PATIENTS AND METHODS: The case notes of three Caucasian patients with BP who presented to our tertiary referral centre were reviewed. Their case histories, investigations and managements are presented. A search of MEDLINE, PubMed and Cochrane databases was performed to review relevant literature around BP.
DISCUSSION: BP is a rare condition characterised by multiple papillary adenomas involving the biliary tree which lead to recurrent attacks of cholangitis. It is a low-grade neoplasm with high malignant potential and should be regarded as a pre-malignant lesion.

PMID: 22154963 [PubMed - indexed for MEDLINE]
Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: surgical approaches and outcomes.
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Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: surgical approaches and outcomes.

J Am Coll Surg. 2012 Feb;214(2):174-83

Authors: Young AL, Adair R, Prasad KR, Toogood GJ, Lodge JP

Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) most commonly arises in patients with chronic liver disease. Data on outcomes after liver resection in patients with noncirrhotic, nonfibrotic, seronegative, referred to as a "normal" liver are limited. We aimed to investigate differences in prognostic factors and outcomes between patients presenting with HCC arising in "normal" liver (NLHCC) and that arising in "diseased" liver (DLHCC).
STUDY DESIGN: All patients undergoing resection for HCC between 1994 and 2008 were assessed. Multivariable analysis of clincopathologic data from the NLHCC group was performed by comparing them with data from the group who had surgery for DLHCC during this period.
RESULTS: During the 15-year study period, 142 patients underwent liver resection for HCC: 81 for NLHCC and 61 for DLHCC. NLHCCs were more often solitary but were larger and required more major resections. There was no significant difference in survival outcomes between patients who had NLHCC or DLHCC, with overall and recurrence-free 5-year survivals of 60% and 51% in NLHCC and 55% and 33% in DLHCC, respectively. In patients with NLHCC, significant factors predicting overall survival were blood transfusion requirement (p = 0.003) and age (p = 0.009), and the only significant factor at predicting recurrence-free survival was presence of multiple tumors (p = 0.025). In contrast, in DLHCC, the only significant prognostic variables were a preoperative tumor biopsy (p = 0.017) or a high neutrophil-to-lymphocyte ratio (p = 0.001), both of which predicted a poorer recurrence-free survival.
CONCLUSIONS: HCC presenting in patients with a normal background liver parenchyma appears to present a different spectrum of the disease. However, excellent outcomes can be achieved after liver resection, although this often requires the use of advanced techniques due to late presentation.

PMID: 22137823 [PubMed - indexed for MEDLINE]
Inferior vena cava resection with hepatectomy: challenging but justified.
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Inferior vena cava resection with hepatectomy: challenging but justified.

HPB (Oxford). 2011 Nov;13(11):802-10

Authors: Malde DJ, Khan A, Prasad KR, Toogood GJ, Lodge JP

Abstract
OBJECTIVE: The aim of this study was to evaluate the clinical outcome of hepatectomy combined with inferior vena cava (IVC) resection and reconstruction for treatment of invasive liver tumours.
METHODS: From February 1995 to September 2010, 2146 patients underwent liver resections in our hospital's hepatopancreatobiliary unit. Of these, 35 (1.6%) patients underwent hepatectomy with IVC resection. These patients were included in this study. Data were analysed from a prospectively collected database.
RESULTS: Resections were carried out for colorectal liver metastasis (CRLM) (n= 21), hepatocellular carcinoma (n= 6), cholangiocarcinoma (n= 3) and other conditions (n= 5). Resections were carried out with total vascular occlusion in 34 patients and without in one patient. In situ hypothermic perfusion was performed in 13 patients; the ante situm technique was used in three patients, and ex vivo resection was used in six patients. There were four early deaths from multiple organ failure. Postoperative complications occurred in 14 patients, three of whom required re-operation. Median overall survival was 29 months and cumulative 5-year survival was 37.7%. Rates of 1-, 2- and 5-year survival were 75.9%, 58.7% and 19.6%, respectively, in CRLM patients.
CONCLUSIONS: Aggressive surgical management of liver tumours with IVC involvement offers the only hope for cure in selected patients. Resection by specialist teams affords acceptable perioperative morbidity and mortality rates.

PMID: 21999594 [PubMed - indexed for MEDLINE]
Transplantation of solid organs procured from influenza A H1N1 infected donors.
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Transplantation of solid organs procured from influenza A H1N1 infected donors.

Transpl Int. 2011 Dec;24(12):e107-10

Authors: Cockbain AJ, Jacob M, Ecuyer C, Hostert L, Ahmad N

Abstract
Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.

PMID: 21954984 [PubMed - indexed for MEDLINE]
Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: a review and consensus statement.
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Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: a review and consensus statement.

Liver Transpl. 2011 Oct;17 Suppl 2:S81-9

Authors: Prasad KR, Young RS, Burra P, Zheng SS, Mazzaferro V, Moon DB, Freeman RB

PMID: 21748847 [PubMed - indexed for MEDLINE]
Evolution of the surgical management of perihilar cholangiocarcinoma in a Western centre demonstrates improved survival with endoscopic biliary drainage and reduced use of blood transfusion.
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Evolution of the surgical management of perihilar cholangiocarcinoma in a Western centre demonstrates improved survival with endoscopic biliary drainage and reduced use of blood transfusion.

HPB (Oxford). 2011 Jul;13(7):483-93

Authors: Young AL, Igami T, Senda Y, Adair R, Farid S, Toogood GJ, Prasad KR, Lodge JP

Abstract
BACKGROUND: Perihilar cholangiocarcinoma (PHCCA) remains a surgical challenge for which few large Western series have been reported. The aims of this study were to investigate the results of surgical resection for PHCCA and assess how practice has evolved over the past 15 years.
METHODS: A prospectively maintained database was interrogated to identify all resections. Clinicopathological data were analysed for impact on survival. Subsequently, data for resections carried out during the periods 1994-1998, 1999-2003 and 2004-2008 were compared.
RESULTS: Eighty-three patients underwent resection. Trisectionectomy was required in 67% of resections. Overall survival was 70%, 36% and 20% at 1, 3 and 5 years, respectively. Size of tumour, margin (R0) status, lymph node status, distant metastasis, tumour grade, portal vein resection, microscopic direct vascular invasion, T-stage and blood transfusion requirement significantly affected outcome on univariate analysis. Distant metastasis (P = 0.040), percutaneous biliary drainage (P = 0.015) and blood transfusion requirement (P = 0.026) were significant factors on multivariate analysis. Survival outcomes improved and blood transfusion requirement was significantly reduced in the most recent time period.
DISCUSSION: Blood transfusion requirement and preoperative percutaneous biliary drainage were identified as independent indicators of a poor prognosis following resection of PHCCA. Longterm survival can be achieved following the aggressive surgical resection of this tumour, but the emergence of a clear learning curve in our analyses indicates that these patients should be managed in high-volume centres in order to achieve improved outcomes.

PMID: 21689232 [PubMed - indexed for MEDLINE]
Budd-Chiari syndrome--a review of the diagnosis and management.
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Budd-Chiari syndrome--a review of the diagnosis and management.

Acute Med. 2011;10(1):5-9

Authors: Fox MA, Fox JA, Davies MH

Abstract
Budd-Chiari syndrome (BCS) is the liver disease resulting from hepatic venous outflow obstruction comprising a triad of abdominal discomfort, hepatomegaly and ascites. Advances in the management of this disorder over the last three decades have dramatically improved survival. We present a review of the management of BCS followed by a case which illustrates some key points in the diagnosis and treatment of this condition.

PMID: 21573256 [PubMed - indexed for MEDLINE]
The impact of postoperative infection on long-term outcomes in liver transplantation.
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The impact of postoperative infection on long-term outcomes in liver transplantation.

Transplant Proc. 2010 Dec;42(10):4181-3

Authors: Cockbain AJ, Goldsmith PJ, Gouda M, Attia M, Pollard SG, Lodge JP, Prasad KR, Toogood GJ

Abstract
INTRODUCTION: Postoperative infection (POI) prolongs inpatient stay, delays return to normal activity, and may be detrimental to long-term survival after cancer resections. This study sought to identify the impact of postoperative infection on liver transplantation outcomes.
METHODS: We analyzed our prospective database of 910 adult patients who underwent liver transplantation between 2000 and 2010 in a single UK center. POI was defined as pyrexia plus positive cultures from blood, sputum, urine, wound, or ascitic fluid. Patient demographic features and perioperative variables were analyzed for their effects on POI. The impacts of POI on overall survival (OS) and graft survival were analyzed using Kaplan-Meier curves with log-rank tests for significance, before entry into a multivariate regression analysis. We analyzed the effects of POI on the length of hospital stay (LOS) and the incidence of acute rejection episodes and readmissions within 1 year as secondary outcomes.
RESULTS: Patients who developed a postoperative chest or wound infection showed poorer OS at a mean of 7.0 versus 8.8 years (P = .009) and 7.0 versus 8.8 years (P = .003), respectively. Infection in blood, ascitic fluid, or urine showed no significant impact on survival. LOS was significantly increased among patients with a wound (median 21 vs 17 days, P = .011), a sputum (median 24 vs 17 days, P < .001), or a blood infection (median 32 vs 17 days, P < .001). Higher rates of intraoperative blood transfusion were observed among subjects who developed a chest or a wound infection. There was no difference in other variables between those who did versus did not develop an infection. Upon multivariate analysis, wound infection was the strongest independent predictor of OS (P = .007).
CONCLUSION: We demonstrated that wound or chest infections were associated with poorer OS. More aggressive prophylactic and/or therapeutic interventions targeting specific sites of infection may represent a simple and cost-effective measure to reduce hospital stay and improve OS.

PMID: 21168658 [PubMed - indexed for MEDLINE]
Outcomes following renal transplantation after multiorgan retrieval versus kidney-only retrieval in donation after cardiac death donors.
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Outcomes following renal transplantation after multiorgan retrieval versus kidney-only retrieval in donation after cardiac death donors.

Transplant Proc. 2010 Dec;42(10):3963-5

Authors: Goldsmith PJ, Ridgway DM, Pine JK, Speak G, Newstead C, Lewington AJ, Menon KV, Ahmad N, Attia M

Abstract
With the increase of donation after cardiac death (DCD) now including procurements for not only kidney but also liver, pancreas, and lung transplantations, we analyze whether multiorgan DCD retrievals have a negative impact on immediate and short-term renal transplant outcomes due to increased length of time of explantation of the kidney from the donor and the associated risks of re-warming. We performed a retrospective study of all DCD donors from 2002 to 2009 at a single unit. Immediate and short-term outcomes between kidney-only versus multiorgan retrieval were compared. Cold ischaemia was significant between the two groups (P = .04), but all other variables were nonsignificant. The results show that immediate graft function, rates of acute rejection and graft/recipient survival are comparable when DCD allografts are procured from both multiorgan and kidney-only donors. The comparable outcomes from kidney-only and multiorgan donations in this study may be due to by the highly selective use of donors for multiorgan DCD donation. This selectivity may explain the "better" quality of kidney for these cases in which patients were able to tolerate potentially injurious rewarming.

PMID: 21168600 [PubMed - indexed for MEDLINE]
Outcomes of intensive surveillance after resection of hepatic colorectal metastases.
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Outcomes of intensive surveillance after resection of hepatic colorectal metastases.

Br J Surg. 2010 Oct;97(10):1552-60

Authors: Gomez D, Sangha VK, Morris-Stiff G, Malik HZ, Guthrie AJ, Toogood GJ, Lodge JP, Prasad KR

Abstract
BACKGROUND: The impact of computed tomography (CT)-based follow-up for the detection of resectable disease recurrence following surgery for colorectal liver metastases (CRLM) was evaluated.
METHODS: Some 705 patients undergoing resection of CRLM between January 1993 and March 2007 were included. Surveillance comprised 3-monthly CT (thorax, abdomen and pelvis) in the first 2 years after surgery, 6 monthly for 3 years and annually from years 6 to 10. Survival differences following recurrence between patients managed surgically and palliatively were determined, and the cost was calculated.
RESULTS: Five-year disease-free and overall survival rates were 28.3 and 32.3 per cent respectively. Of 402 patients who developed recurrence within 2 years, 88 were treated with liver resection alone and 36 with lung and/or liver resection. Their 5-year overall survival rates were 31 and 30 per cent respectively, compared with 3.9 per cent in 278 patients managed palliatively (P < 0.001). For each 3-month interval during the first year of follow-up, patients with recurrence treated surgically had better overall survival than those treated palliatively. The cost of surveillance that identified 124 patients amenable to further resection was 12,338 pounds per operated recurrence. Assuming that patients with recurrence gained 5 years' survival, the mean survival gain was 4.28 years per resection and the cost per life-year gained was 2883 pounds.
CONCLUSION: Intensive 3-monthly CT surveillance after liver resection for CRLM detects recurrence that is amenable to further resection in a considerable number of patients. These patients have significantly better survival with a reasonable cost per life-year gained.

PMID: 20632325 [PubMed - indexed for MEDLINE]
Interaction of tumour biology and tumour burden in determining outcome after hepatic resection for colorectal metastases.
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Interaction of tumour biology and tumour burden in determining outcome after hepatic resection for colorectal metastases.

HPB (Oxford). 2010 Mar;12(2):84-93

Authors: Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP, Prasad KR

Abstract
AIMS: To determine the outcome of colorectal liver metastasis (CRLM) patients based on tumour burden, represented by tumour number and size, and tumour biology as assessed by an inflammatory response to tumour (IRT) and margin positivity.
METHODS: Data were collated from CRLM patients undergoing resection from January 1993 to March 2007. Patients were divided into: low (<or=3 metastases and/or <or=3 cm); moderate (4-7 metastases and/or >3-<or=5 cm); and high (>or=8 metastases and/or >5 cm) tumour burden.
RESULTS: Seven hundred and five patients underwent resection, of which 154 (21.8%), 262 (37.2%) and 289 (41.0%) patients were in the low, moderate and high tumour burden groups, respectively. The 5-year disease-free (P < 0.001) and overall (P < 0.001) survival were significantly different between the groups. IRT (P < 0.001), extent of resection (P < 0.001) and margin (P < 0.001) also differed between the groups. Sub-group analysis revealed that IRT was the only adverse predictor for disease-free and overall survival in the low group. In the moderate group, IRT predicted poorer disease-free survival on multi-variate analysis. In the high group, R1 resection and transfusion were predictors of poorer disease-free survival and age >or=65 years, R1 resection and IRT were adverse predictors of overall survival.
CONCLUSION: Resection margin influenced the outcome of patients with high tumour burden, hence the importance of achieving clear margins. IRT influenced the outcome of patients with less aggressive disease.

PMID: 20495651 [PubMed - indexed for MEDLINE]
Predictors of blood transfusion requirement in elective liver resection.
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Predictors of blood transfusion requirement in elective liver resection.

HPB (Oxford). 2010 Feb;12(1):50-5

Authors: Cockbain AJ, Masudi T, Lodge JP, Toogood GJ, Prasad KR

Abstract
BACKGROUND: Liver resection remains major surgery frequently requiring intra-operative blood transfusion. Patients are typically over cross-matched, and with blood donor numbers falling, cross-matching and transfusion policies need rationalizing.
AIM: To identify predictors of peri-operative blood transfusion.
METHODS: A retrospective review of elective hepatic resections over a 4-year period was performed. Twenty-six variables including clinicopathological variables and intra-operative data were collated, together with the number of units of blood cross-matched and transfused in the immediate peri-operative period (48 h). Multivariate regression analysis was performed to identify independent predictors of blood transfusion, and a Risk Score for transfusion constructed.
RESULTS: Five hundred and eighty-nine patients were included in the study, and were cross-matched with a median 10 units of blood. Seventeen per cent of patients received a blood transfusion; median transfusion when required was 2 units. Regression analysis identified seven factors predictive of transfusion: haemoglobin <12.5 g/dL, pre-operative biliary drainage, coronary artery disease, largest tumour >3.5 cm, cholangiocarcinoma, redo resection and extended resection (5+ segments). Patients were stratified into high or low risk of transfusion based on Risk Score with a sensitivity of 73% [receiver-operating characteristic (ROC) 0.77].
CONCLUSIONS: Patients undergoing elective liver resection are over-cross-matched. Patients can be classified into high and low risk of transfusion using a Risk Score, and cross-matched accordingly.

PMID: 20495645 [PubMed - indexed for MEDLINE]
An unusual case of irregular dilated ducts post-liver transplant.
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An unusual case of irregular dilated ducts post-liver transplant.

Liver Int. 2011 Feb;31(2):229

Authors: Goldsmith PJ, Ridgway DM, Prasad KR, Attia M

PMID: 20345697 [PubMed - indexed for MEDLINE]
Liver histopathology in the Yorkshire region: a network model.
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Liver histopathology in the Yorkshire region: a network model.

J Clin Pathol. 2009 Dec;62(12):1141-3

Authors: Reall G, Jones RL, Wyatt JI

Abstract
AIM: To investigate the volume and provision of local liver histopathology in the 11 hospitals of the Yorkshire region outside Leeds, as a potential model for a hepatopathology network.
METHODS: Postal questionnaire to all histopathologists in 11 hospital trusts in Yorkshire.
RESULTS: Liver biopsies represent about 0.5% histopathology requests in Yorkshire, with more medical than tumour biopsies. Pathologists often discuss these biopsies with each other and clinicians; a third had done liver continuing professional development (CPD) in the last 3 years, and 70% would like to do more. Overall, around 5% liver biopsies are reviewed in the hepatology centre, and most responders thought this about right.
CONCLUSIONS: For primary reporting of liver biopsies, local pathologists need good communication with the responsible clinician, access to relevant CPD in liver pathology and a biopsy referral pathway for cases which are clinically or pathologically challenging.

PMID: 19946102 [PubMed - indexed for MEDLINE]
Surgical treatment of hilar cholangiocarcinoma in a new era: comparison among leading Eastern and Western centers, Leeds.
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Surgical treatment of hilar cholangiocarcinoma in a new era: comparison among leading Eastern and Western centers, Leeds.

J Hepatobiliary Pancreat Sci. 2010 Jul;17(4):497-504

Authors: Young AL, Prasad KR, Toogood GJ, Lodge JP

Abstract
OBJECTIVE: Surgery for hilar cholangiocarcinoma (HCCA) remains challenging, with radical procedures thought to offer the best chance of long-term survival. Here we present our data for surgical resection of HCCA for the period 2001-2008.
METHODS: A prospectively maintained database was interrogated to identify all resections. Clinico-pathological data were analyzed and assessed for impact on survival.
RESULTS: 51 patients were identified. Almost three-quarters required hepatic trisectionectomy. Overall survival was 76% at 1 year, 36% at 3 years and 20% at 5 years. When R0 resection was achieved, the 5-year survival was 40%. Portal vein resection, perineural invasion and T-stage were predictive of overall survival on univariate analysis. Only T-stage remained significant on multivariate analysis. Lymph node status predicted disease-free survival.
CONCLUSION: Radical surgery continues to offer the prospect of long-term survival for patients with HCCA. Earlier detection and referral to tertiary centers may allow more patients to have potentially curative surgical resections.

PMID: 19859651 [PubMed - indexed for MEDLINE]
Correlation between postoperative infective complications and long-term outcomes after hepatic resection for colorectal liver metastasis.
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Correlation between postoperative infective complications and long-term outcomes after hepatic resection for colorectal liver metastasis.

Ann Surg. 2010 Jan;251(1):91-100

Authors: Farid SG, Aldouri A, Morris-Stiff G, Khan AZ, Toogood GJ, Lodge JP, Prasad KR

Abstract
BACKGROUND: The impact of postoperative morbidity, and in particular infective complications on long-term outcomes, following hepatic resection for colorectal liver metastasis (CRLM) is not widely published.
OBJECTIVE: To evaluate the effect of postoperative complications on disease recurrence and overall survival in patients undergoing hepatic resection for CRLM.
METHODS: All patients undergoing hepatic resection for CRLM from January 1993 and March 2007 were identified, and postoperative complications analyzed. Patients who died of postoperative complications within 30 days of surgery were excluded form the study. Postoperative complications were graded using a validated system of classification. Complications were further classified into infective and noninfective complication groups and the primary end points of the study were disease free survival (DFS) and overall survival (OS) at 5 years.
RESULT: A total of 705 patients underwent hepatic resection in the study period. Median follow-up was 38 months. Operative morbidity and mortality were 28% and 3.6%, respectively. The total number of patients was 197 (28%) with complications, and 508 (72%) without complications. The 5 year DFS and OS for those with and without complications were: 13% versus 26% (P < 0.001) and 24% versus 37% (P < 0.001), respectively. Multivariate analysis showed inflammatory response to tumor score, blood transfusion, tumor number >8, and postoperative sepsis to be independent factors associated with DFS, and inflammatory response to tumor, tumor number >8, and postoperative sepsis to be independent predictors for OS. Intra-abdominal and respiratory infection but not wound infections were associated with poorer long-term outcomes.
CONCLUSIONS: Postoperative complications influence long-term outcomes in hepatic resection for CRLM. Specifically, postoperative sepsis is an independent predictor of disease free and overall survival. Thorough preoperative optimization, meticulous surgical technique and careful management in the postoperative period may reduce the incidence of these complications and influence long-term outcomes.

PMID: 19858702 [PubMed - indexed for MEDLINE]
Do smaller adults wait longer for liver transplantation? A comparison of the UK and the USA data.
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Do smaller adults wait longer for liver transplantation? A comparison of the UK and the USA data.

Clin Transplant. 2010 Mar-Apr;24(2):181-7

Authors: Young AL, Peters CJ, Pocock PV, Millson CE, Prasad KR

Abstract
BACKGROUND: The number of patients on the UK and the USA liver transplant list is increasing. As size match is an important factor in the UK organ allocation, we studied the effect of recipient size on liver transplantation in the UK and the USA.
METHODS: The UK Transplant and United Network for Organ Sharing databases were used to assess difference in access to transplantation between smaller adult patients and their larger counterparts over three time periods. Subsequently, proportions of split, NHBD and living-donor transplants were analyzed.
RESULTS: There were 1576 UK and 29,150 USA patients in our analysis. The UK small patients have been significantly disadvantaged in access to transplantation particularly in early years and in adult only transplant units. This contrasts to the USA where smaller patients have never been disadvantaged and transplantation rates are steadily increasing. Split-liver transplants are being carried out in increasing numbers in the UK but not the USA.
CONCLUSIONS: Small adults are still less likely to be transplanted at six months in adult only units in the UK. The lack of size matched organs for smaller adults and the overall decrease in rates of transplantation in the UK may be remedied by careful consideration of allocation policy and increased use of innovative techniques.

PMID: 19681972 [PubMed - indexed for MEDLINE]
Case hepatic endometriosis: a continuing diagnostic dilemma.
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Case hepatic endometriosis: a continuing diagnostic dilemma.

HPB Surg. 2009;2009:407206

Authors: Goldsmith PJ, Ahmad N, Dasgupta D, Campbell J, Guthrie JA, Lodge JP

Abstract
BACKGROUND: Intraparenchymal endometriosis of liver is rare. It may present as liver tumour and the diagnosis is not usually established till after surgery.
CASE OUTLINE: A 48-year-old postmenopausal woman presented with right upper quadrant pain and a cystic liver mass. Liver function tests and tumour markers (alphaFP, CEA, CA 19-9, and CA 125) were normal. Radiological imaging (USS, CT and MRI) suggested a thick walled cystic mass involving segments IV and VIII with complex intracystic septations. Frozen section at operation suggested a benign cystadenoma. The cyst was enucleated using a CUSA (Cavitron ultrasonic aspirator). The final histology confirmed endometriosis.
DISCUSSION: Eleven cases of hepatic endometrioma have been reported and only four in postmenopausal women. Preoperative diagnosis poses a challenge and so far none of the cases have been diagnosed preoperatively. Surgery remains the treatment of choice. Accurate diagnosis at time of operation may avoid extensive liver surgery and its associated morbidity.

PMID: 19587832 [PubMed - indexed for MEDLINE]
Donor risk index and MELD interactions in predicting long-term graft survival: a single-centre experience.
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Donor risk index and MELD interactions in predicting long-term graft survival: a single-centre experience.

Transplantation. 2009 Jun 27;87(12):1858-63

Authors: Bonney GK, Aldersley MA, Asthana S, Toogood GJ, Pollard SG, Lodge JP, Prasad KR

Abstract
INTRODUCTION: Feng et al. described the donor risk index (DRI) in North American liver transplant recipients. We evaluated the effect of the DRI and model for end-stage liver disease (MELD) score on liver transplant recipients from a single center in the United Kingdom.
METHOD: Prospectively, collected data of all patients transplanted at our center between January 1995 and December 2005 were included in the analysis (n=1090). Outcomes evaluated included patient-censored and death-censored graft survival. Outcomes of liver transplantation from "high" and "low" DRI groups (> or =1.8 and <1.8, respectively) on patients categorized into low (<15), intermediate (15-30), and high (>30) MELD categories were analyzed.
RESULTS: MELD at transplant was the only significant predictor of patient survival. MELD at transplant and DRI more than 1.7 were associated with a poorer graft survival (P=0.03). There was a trend toward poorer graft survival in high DRI grafts transplanted in low and "intermediate" MELD categories (P=0.47 and 0.006, respectively). However, in the high MELD category, there was a similar graft survival for both high and low DRI grafts.
CONCLUSION: Patients with low and intermediate MELDs at transplantation may be better served by a low DRI graft, whereas patients with high MELD may not be compromised by receiving a high DRI graft.

PMID: 19543065 [PubMed - indexed for MEDLINE]
Inflammatory pseudotumours of the liver: a spectrum of presentation and management options.
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Inflammatory pseudotumours of the liver: a spectrum of presentation and management options.

Eur J Surg Oncol. 2009 Dec;35(12):1295-8

Authors: Goldsmith PJ, Loganathan A, Jacob M, Ahmad N, Toogood GJ, Lodge JP, Prasad KR

Abstract
PURPOSE: To review the current management options in inflammatory pseudotumours via analysis of ten cases from this unit the largest experience of this pathology in a Western series. To assess the medical and operative options available for this condition and the varying outcomes and the lessons learned in this unit over the time period.
RESULTS: Data from the ten cases were analysed and a comprehensive review of the published literature to date has detailed 128 case reports with 215 cases of inflammatory pseudotumour of the liver. Data analysed included patient demographics, diagnostic modalities, details of treatment and eventual outcome. The data was tabulated using an Excel spreadsheet (Microsoft Excel 2004 for Mac 2004.Version 11.0). Categorical variables were compared using Pearson's chi(2) test and p values <0.05 were defined as statistically significant. Statistical analysis was performed using SPSS for Windows (Version 9.0, SPSS Inc., Chicago, IL).
CONCLUSION: Emphasis is placed on a preferred medical management initially for this tumour with a good prognosis coupled with regular follow up. There may be a need for surgical resection cases where diagnosis is unclear or the patient is not responding to medical treatment with progression of disease or symptoms.

PMID: 19515527 [PubMed - indexed for MEDLINE]
The missing stone.
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The missing stone.

Liver Int. 2010 Jan;30(1):76

Authors: Goldsmith P, Prasad KR

PMID: 19291179 [PubMed - indexed for MEDLINE]
Laparoscopic left lateral sectionectomy: surgical technique and our results from Leeds.
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Laparoscopic left lateral sectionectomy: surgical technique and our results from Leeds.

J Laparoendosc Adv Surg Tech A. 2009 Feb;19(1):29-32

Authors: Khan AZ, Prasad KR, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Although laparoscopic left lateral sectionectomy is increasingly becoming the accepted approach for resection of tumors in hepatic segments II and III, the variations in surgical technique exist.
METHODS: Our technique relies on mobilization of the left lateral sector followed by extracorporeal control of the portal pedicle allowing intermittent occlusion when needed. The parenchyma is thinned, exposing the inflow and outflow allowing application of endoscopic staplers under direct vision for parenchymal transection.
RESULTS: Eleven patients underwent left lateral sectionectomy between 2000 and November 2007 and had a median postoperative stay of 3 days. Two patients had to be converted early on.
CONCLUSION: Left lateral sectionectomy using this approach appears to be safe and reproducible, and this technique should be considered for patients with tumors in hepatic segments II and III.

PMID: 19226228 [PubMed - indexed for MEDLINE]
Successful treatment of cerebral tuberculosis in a liver transplant recipient.
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Successful treatment of cerebral tuberculosis in a liver transplant recipient.

Liver Transpl. 2009 Feb;15(2):260-2

Authors: Asthana S, Bonney GK, Guthrie A, Davies MH, Prasad KR

PMID: 19177444 [PubMed - indexed for MEDLINE]
A simple prophylaxis regimen for MRSA: its impact on the incidence of infection in patients undergoing liver resection.
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A simple prophylaxis regimen for MRSA: its impact on the incidence of infection in patients undergoing liver resection.

Ann R Coll Surg Engl. 2009 Jan;91(1):35-8

Authors: Al-Mukhtar A, Wong VK, Malik HZ, Abu-Hilal M, Denton M, Wilcox M, Lodge JP, Toogood GJ, Prasad KR

Abstract
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infection has increased at an alarming rate in the recent past and has major cost implications. The aim of this study is to assess the impact of a policy of pre-operative MRSA prophylaxis on the incidence of MRSA infection in patients undergoing liver resection.
PATIENTS AND METHODS: A total of 585 patients underwent hepatectomy in a tertiary referral centre between January 2000 and September 2005. In September 2003, a policy of MRSA prophylaxis (nasal mupirocin and triclosan wash for 5 days) was introduced within this unit. Demographic, pathological and outcome data were compared between the pre- and post-MRSA prophylaxis cohorts.
RESULTS: The prevalence of MRSA infection prior to initiating the prophylaxis protocol was 29 patients (8.3%) and this fell to 9 patients (3.8%; P = 0.029). Furthermore, patients who had MRSA-related infection had a higher incidence of additional complications compared to the rest of the cohort (P = 0.001). Total cost savings incurred as a result of this protocol over the past 2 years has been approximated at 28,893 pounds.
CONCLUSIONS: Introduction of a simple MRSA prophylaxis policy has had a significant reduction on the incidence MRSA-related infection within our patient population, leading to reduced morbidity and cost saving to the UK National Health Service.

PMID: 19126333 [PubMed - indexed for MEDLINE]
Surgical management of hepatocellular carcinoma: is the jury still out?
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Surgical management of hepatocellular carcinoma: is the jury still out?

Surg Oncol. 2009 Dec;18(4):298-321

Authors: Morris-Stiff G, Gomez D, de Liguori Carino N, Prasad KR

Abstract
INTRODUCTION: Hepatocellular carcinoma (HCC) is currently the fifth most common neoplasm worldwide. The only therapies which are capable of providing cure are hepatic resection and liver transplantation. Results from either resection or transplantation show 5-year survival rates of up to 70% in selected patients. Patient assessment is key to selecting candidates for surgery be it resection or transplantation.
METHODS: A search was performed of the English Medline database for the period 1997-2006 using the MeSH headings: hepatocellular carcinoma, liver resection, and liver transplantation, with the main analysis concentrated on survival data for all patients undergoing resection or transplantation.
RESULTS: There is a large variation in the mortality and recurrence rate following resection/transplantation due to differences in definition in different series. The median perioperative (30 day/in-hospital) mortality rate following resection was a median of 4.7%. The median 1, 3 and 5 year overall survival rates were 80.1%, 55% and 37.1%, respectively. The disease-free survivals at identical time intervals were 64%, 38% and 27%. The median 30 day mortality following liver transplant was 4.7% and the median 3-month mortality was 13.3%. The median overall 1, 3, and 5-year survival rates were 80.9%, 70.2% and 62%, respectively, whilst the disease-free survivals at identical time intervals were 79%, 62.5% and 54.5%. Several risk factors for overall and/or disease-free survival following resection and transplantation were found in those papers where a multivariate analysis was included.
DISCUSSION: A possible algorithm would be to perform resection for patients with preserved liver function and offer transplantation to those of Child-Pugh status B or C who fit within Milan criteria. If recurrence occurred after resection or underlying liver disease progresses, salvage transplants may be performed.
CONCLUSION: The current evidence base for resection and transplantation in the treatment of HCC is inadequate to provide a definite answer as to which is optimal therapy and a randomised controlled trial to compare the outcomes of resection and transplantation is now required.

PMID: 19062271 [PubMed - indexed for MEDLINE]
Epidural analgesia and liver resection: postoperative coagulation disorders and epidural catheter removal.
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Epidural analgesia and liver resection: postoperative coagulation disorders and epidural catheter removal.

Minerva Anestesiol. 2011 Jul;77(7):671-9

Authors: Stamenkovic DM, Jankovic ZB, Toogood GJ, Lodge JP, Bellamy MC

Abstract
BACKGROUND: The aim of this study was to quantify the duration and severity of postoperative coagulopathy in order to establish the optimal time for epidural catheter removal.
METHODS: In a 2-year retrospective study, 140 consecutive patients underwent major liver resection.
RESULTS: Epidural catheters were present in 123 patients (87.9%). Resections were: 33 (26.8%) right hepatectomy (with or without left metastasectomy), 9 (7.3%) left hemihepatectomy (with or without right metastasectomy), 37 (30.1%) trisectionectomy (extended hemihepatectomy) and 44 (35.8%) non-anatomical metastasectomy. Surgery was quantified by segments resected (4 [range: 1-7]). Vascular inflow occlusion was used in 65.6%. Ischaemic time was 26.5 min (range: 0-104 min). Platelet count fell postoperatively and was lowest on day 2 (205±72 10(9) L(-1)). There was a significant increase in prothrombin time, activated partial thromboplastin time and International Normalised Ratio (INR) postoperatively, peaking on day 2 (21.5±5.6 s, 37.9±5.8 s and 1.9±0.5, respectively). Changes persisted beyond day 6. Epidural catheters were removed on day 5 (1-11), with a protocol criterion of INR <1.2. Actual INR on day 5 was 1.49±0.36.
CONCLUSION: Despite this, no epidural or spinal haematoma was recorded.

PMID: 19037193 [PubMed - indexed for MEDLINE]
Thrombotic complications following liver resection for colorectal metastases are preventable.
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Thrombotic complications following liver resection for colorectal metastases are preventable.

HPB (Oxford). 2008;10(5):311-4

Authors: Morris-Stiff G, White A, Gomez D, Toogood G, Lodge JP, Prasad KR

Abstract
BACKGROUND: Surgery for colorectal liver metastases (CRLM) can be expected to be associated with a significant rate of thromboembolic complications due to the performance of long-duration oncologic resections in patients aged 60 years.
AIMS: To determine the prevalence of clinically significant thrombotic complications, including deep venous thrombosis (DVT) and pulmonary embolus (PE), in a contemporary series of patients undergoing resection of CRLM with standard prophylaxis.
MATERIAL AND METHODS: A prospectively maintained database identified patients undergoing resection of CRLM from January 2000 to March 2007 and highlighted those developing thromboembolic complications. In addition, the radiology department database was reviewed to ensure that clinically suspicious thromboses had been confirmed radiologically by ultrasound in the case of DVT or computed tomography for PEs.
RESULTS: During the period of the study, 523 patients (336 M and 187 F) with a mean age of 65 years underwent resection. A major hepatectomy was performed in 59.9%. One or more complications were seen in 45.1% (n=236) of patients. Thrombotic complications were seen in 11 (2.1%) patients: DVT alone (n=4) and PE (n=7). Eight of 11 thrombotic complications occurred in patients undergoing major hepatectomy, 4 of which were trisectionectomies. Patients were anti-coagulated and there were no mortalities.
CONCLUSIONS: The symptomatic thromboembolic complication rate was lower in this cohort than may be expected in patients undergoing non-hepatic abdominal surgery. It is uncertain whether this is due entirely to effective prophylaxis or to a combination of treatment and a natural anti-coagulant state following hepatic resection.

PMID: 18982144 [PubMed]
Portal vein arterialization as a salvage procedure during left hepatic trisectionectomy for hilar cholangiocarcinoma.
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Portal vein arterialization as a salvage procedure during left hepatic trisectionectomy for hilar cholangiocarcinoma.

J Am Coll Surg. 2008 Nov;207(5):e1-6

Authors: Young AL, Prasad KR, Adair R, Abu Hilal M, Guthrie JA, Lodge JP

PMID: 18954768 [PubMed - indexed for MEDLINE]
The reduced left lateral segment in pediatric liver transplantation: an alternative to the monosegment graft.
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The reduced left lateral segment in pediatric liver transplantation: an alternative to the monosegment graft.

Pediatr Transplant. 2008 Sep;12(6):696-700

Authors: Attia MS, Stringer MD, McClean P, Prasad KR

Abstract
Tailoring graft size to small paediatric recipients is a challenge. We have developed a reduced left lateral segment as an alternative to monosegment transplantation for small size recipients. Since November 2000, 89 children have been transplanted with 100 deceased donor liver grafts in our unit. Our median patient and graft survival is 89% and 88% respectively. Four of these cases were performed using a new technique of creating a small donor graft by reducing the left lateral segment. The median weight of the reduced liver graft was 264 g (range: 165-390 g). The median blood transfusion requirement was 101 mL/kg body weight (range 69-167 mL/kg). The median values of peak ALT were 1473 IU/L, INR 2.2 and bilirubin 293 micromol/L in the first two wk following surgery. One neonatal recipient died five days after transplantation from a massive intracranial haemorrhage despite satisfactory graft function. Another recipient with excellent graft function died 10 months later from primary pulmonary hypertension and secondary cardiac failure. Hepatic artery thrombosis occurred in one patient with successful revascularization but he was retransplanted three months later for chronic rejection. No biliary or venous outflow complications occurred in this group. This technique of reduced left lateral segment liver transplantation is an alternative to the monosegment graft and allows small recipients to be successfully transplanted with few technical complications related to graft preparation.

PMID: 18786070 [PubMed - indexed for MEDLINE]
The case for adjuvant chemotherapy. Against.
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The case for adjuvant chemotherapy. Against.

Ann R Coll Surg Engl. 2008 Sep;90(6):454-5

Authors: Khan AZ, Toogood GJ

PMID: 18777622 [PubMed - indexed for MEDLINE]
Outcomes in right liver lobe transplantation: a matched pair analysis.
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Outcomes in right liver lobe transplantation: a matched pair analysis.

Transpl Int. 2008 Nov;21(11):1045-51

Authors: Bonney GK, Aldouri A, Attia M, Lodge PA, Toogood GJ, Pollard SG, Prasad R

Abstract
Split liver transplantation (SLT) has proven to be an effective technique of increasing the donor pool and thereby reducing adult and paediatric waiting list mortality. There remains concern regarding complications in adult recipients. Here, we compare SLT with matched whole liver grafts. Adult recipients of primary extended right lobe grafts (ERL) were matched to recipients of whole liver transplantations (WLTs) according to the following criteria: model of end-stage liver disease (MELD) score, recipient age, indication for liver transplantation and year of transplantation. Twenty-seven pairs of recipients were transplanted for chronic liver disease. The overall 30-day patient survival rates after ERL and WLT were 88.9% and 92.5% and 3-year survival rates after SLT and WLT were 77.8% and 85.2% respectively (log-rank = 0.38). Two patients with SLTs had hepatic artery thromboses and were retransplanted with none from the WLT group. The prevalence of a biliary leak was higher among the SLT group (n = 4) compared with none in the WLT group (P = 0.05). Patients with preoperative hyponatraemia showed a trend towards poorer survival after SLT compared with WLT. Our data suggest that SLT with extended right liver lobes, although not significantly different, shows a trend towards a poorer outcome.

PMID: 18662370 [PubMed - indexed for MEDLINE]
Surgical technique and systemic inflammation influences long-term disease-free survival following hepatic resection for colorectal metastasis.
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Surgical technique and systemic inflammation influences long-term disease-free survival following hepatic resection for colorectal metastasis.

J Surg Oncol. 2008 Oct 1;98(5):371-6

Authors: Gomez D, Morris-Stiff G, Wyatt J, Toogood GJ, Lodge JP, Prasad KR

Abstract
BACKGROUND: To date, there is limited data available on prognostic factors that influence long-term disease-free survival following hepatic resection for colorectal liver metastasis (CRLM). The aim of the study was to identify prognostic factors that were associated with long-term disease-free survival (>5 years) following resection for CRLM.
METHODS: Patients undergoing resection for CRLM from January 1993 to March 2007 were identified from the hepatobiliary database. Data analyzed included demographics, laboratory results, operative findings and histopathological data.
RESULTS: Seven hundred five curative primary hepatic resections were performed, of which 434 patients developed disease recurrence within 5 years and 67 patients were disease-free more than 5 years. There was a significant association between systemic inflammatory response (raised neutrophil to lymphocyte ratio and/or C-reactive protein), blood transfusion, >2 tumors, bilobar disease and resection margin involvement with developing recurrence during the follow-up period. On multivariate analysis, three independent predictors for recurrent disease within the 5-year follow-up were identified: pre-operative inflammatory response; blood transfusion requirement; and status of resection margin.
CONCLUSION: Absence of a systemic inflammatory response and surgical technique to minimize transfusion requirements and obtain a R0 resection margin, are associated with long-term disease-free survival.

PMID: 18646038 [PubMed - indexed for MEDLINE]
The impact of caudate lobe involvement after hepatic resection for colorectal metastases.
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The impact of caudate lobe involvement after hepatic resection for colorectal metastases.

Eur J Surg Oncol. 2009 May;35(5):510-4

Authors: Khan AZ, Wong VK, Malik HZ, Stiff GM, Prasad KR, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Hepatic resections involving the caudate lobe are technically challenging with results from some centers indicating inferior outcomes. We assessed outcomes following hepatic resection for colorectal metastases involving the caudate lobe in a tertiary care center.
METHODS: Operative and oncological data from a prospectively maintained database were analyzed on 687 patients undergoing hepatic resection for colorectal metastases between 1993 and 2006. Patients were analyzed as those with caudate lobe metastases (CLM) and compared with those without caudate lobe involvement (NCLM).
RESULTS: Fifty-two of 687 patients had metastases involving the caudate lobe (8%). Patients with caudate lobe involvement were more likely to require an extended hepatic resection (75% vs 27%, P=0.001), perioperative blood transfusion (29% vs 14%, P=0.002), have a positive resection margin (57% vs 32%, P=0.001) and stay longer in hospital (12 vs 8 days, P=0.001). There was no difference in the complication rates (37% vs 29%) or 30-day mortality between the two groups (2% vs 1%). The median disease free (20 months vs 21 months), and cancer specific survival (42 months vs 59 months) were also similar in the CLM and NCLM groups.
CONCLUSIONS: Although caudate lobe involvement adds to the technical complexity of hepatic resection, these patients can be offered long term survival, similar to other patients with hepatic metastases from colorectal cancer.

PMID: 18644694 [PubMed - indexed for MEDLINE]
Intermittent Pringle manoeuvre is not associated with adverse long-term prognosis after resection for colorectal liver metastases.
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Intermittent Pringle manoeuvre is not associated with adverse long-term prognosis after resection for colorectal liver metastases.

Br J Surg. 2008 Aug;95(8):985-9

Authors: Wong KH, Hamady ZZ, Malik HZ, Prasad R, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long-term outcome after liver resection for colorectal liver metastasis (CRLM).
METHODS: All patients undergoing resection for CRLM in 1993-2006, for whom data on IPM were recorded, were included in the study. A total of 563 patients was available for analysis.
RESULTS: IPM was performed in 289 (51.3 per cent) of the patients. The duration of IPM ranged from 2 to 104 (median 22) min. There were no differences in clinicopathological features or postoperative morbidity between patients who had an IPM and those who did not. The median survival of patients undergoing IPM was 55.7 months compared with 48.9 months in those not having an IPM (P = 0.406). There was no difference in median disease-free survival between the two groups (22.1 versus 19.9 months respectively; P = 0.199).
CONCLUSION: IPM is not associated with an adverse long-term prognosis in patients undergoing liver resection for CRLM.

PMID: 18563791 [PubMed - indexed for MEDLINE]
Quality of life after liver resection for hepatobiliary malignancies.
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Quality of life after liver resection for hepatobiliary malignancies.

Br J Surg. 2008 Jul;95(7):845-54

Authors: Dasgupta D, Smith AB, Hamilton-Burke W, Prasad KR, Toogood GJ, Velikova G, Lodge JP

Abstract
BACKGROUND: Few prospective longitudinal studies have used a validated quality of life (QOL) instrument in patients undergoing liver resection for hepatobiliary malignancy.
METHODS: Patients undergoing liver resection for hepatobiliary tumours in a 1-year period were enrolled. The cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) was completed before operation, and at 6, 12 and 36-48 months after surgery. QOL over time was analysed in relation to several clinical factors.
RESULTS: A total of 103 patients were enrolled. Patient compliance was at least 75 per cent at all stages. Most functional scales and the global QOL scale showed a non-significant trend towards deterioration at 6 months and a return to preoperative level at 12 months. Physical functioning and dyspnoea deteriorated significantly at 6 months (P = 0.020 and P = 0.004 respectively) and did not recover by 12 months (P = 0.002 and P < 0.001 respectively). Pain and fatigue showed clinically significant deterioration over 12 months, which was not statistically significant. Survivors without recurrence at 36-48 months showed better QOL than those with recurrent disease.
CONCLUSION: Major liver resection is associated with acceptable QOL outcomes, and QOL continues to improve in the long term in those without recurrence.

PMID: 18496887 [PubMed - indexed for MEDLINE]
C-reactive protein in liver cancer surgery.
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C-reactive protein in liver cancer surgery.

Eur J Surg Oncol. 2008 Jul;34(7):727-9

Authors: Morris-Stiff G, Gomez D, Prasad KR

Abstract
AIMS: The aim of this article is to review the current state of knowledge with regard to the importance of C-reactive protein (CRP) in patients undergoing hepatic resection for malignancy both in terms of its role as an acute phase reactant and predictor of outcome.
METHODS: An electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles that included the search terms: C-reactive protein; CRP; hepatocellular carcinoma; colorectal liver metastases; hepatic resection; and liver resection.
RESULTS: The limited published data in relation to CRP and liver resection is contradictory. There are studies correlating an acute phase reactant-type postoperative rise in CRP with both good and poor outcome following colorectal liver metastases resection. In relation to prognosis, the only available publication indicates that a high preoperative CRP is a poor prognostic indicator in relation to patient survival. Data for CRP and resection of HCC is equally as limited with early evidence suggesting a correlation between CRP and stage of disease, and documenting an acute temporary elevation in CRP following resection.
CONCLUSIONS: The importance of CRP as a marker of both early postoperative outcome and long-term prognosis in patients with hepatic malignancies is at present unclear. Further studies are required to clarify the changes and more accurately define the mechanism by which CRP is being up-regulated.

PMID: 18356004 [PubMed - indexed for MEDLINE]
Prognostic utility of postoperative C-reactive protein for posthepatectomy liver failure.
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Prognostic utility of postoperative C-reactive protein for posthepatectomy liver failure.

Arch Surg. 2008 Mar;143(3):247-53; discussion 253

Authors: Rahman SH, Evans J, Toogood GJ, Lodge PA, Prasad KR

Abstract
HYPOTHESIS: C-reactive protein (CRP) is an acute-phase protein produced by the liver. We hypothesize that an early dampened CRP response after major liver resection is of prognostic importance in predicting posthepatectomy liver failure (PHLF).
DESIGN: Serum CRP levels were determined on postoperative days 1, 3, and 7 in patients undergoing liver resection (stratified into minor [</=2 segments], standard [3 or 4 segments], and extended [>/=5 segments]). Correlations were made with indices of PHLF (hyperbilirubinemia, coagulopathy, ascites, and encephalopathy), multi-organ dysfunction syndrome, sepsis, and death.
SETTING: Division of Hepatobiliary and Transplant Surgery, Leeds Teaching Hospitals National Health Service Trust, England.
PATIENTS: One hundred thirty-eight individuals who underwent liver resection.
MAIN OUTCOME MEASURES: Sepsis, PHLF, and mortality.
RESULTS: A total of 138 liver resections (39 minor, 51 standard, and 48 extended) were included. Median serum CRP levels on day 1 were significantly lower after extended liver resection (28 mg/L; range, 5-119 mg/L [to convert to nanomoles per liter, multiply by 9.524]) compared with standard resection (41 mg/L; range, 5-85 mg/L) and minor resection (51 mg/L; range, 8-203 mg/L; chi(2) = 19; P < .001). Similar differences were observed on day 3 (chi(2) = 27; P < .001). Postoperative day 1 CRP levels were significantly lower in patients developing PHLF (hyperbilirubinemia, P = .001; ascites, P < .001; coagulopathy, P = .002; and encephalopathy, P < .001) or multiorgan dysfunction syndrome (P = .009) or who died (P = .01). Day 1 serum CRP levels and extent of resection were independent predictors of PHLF in multivariate analysis.
CONCLUSION: The early dampened CRP response after major liver resection may reflect poor hepatic reserve that could have prognostic utility.

PMID: 18347271 [PubMed - indexed for MEDLINE]
Indication for treatment and long-term outcome of focal nodular hyperplasia.
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Indication for treatment and long-term outcome of focal nodular hyperplasia.

HPB (Oxford). 2007;9(5):368-72

Authors: Bonney GK, Gomez D, Al-Mukhtar A, Toogood GJ, Lodge JP, Prasad R

Abstract
INTRODUCTION: Unlike malignant liver tumours, the indications for hepatic resection for benign disease are not well defined. This is particularly true for focal nodular hyperplasia (FNH). Here we summarize a single-centre experience of the diagnosis and management of FNH.
MATERIALS AND METHODS: Using a prospectively collected database, a retrospective analysis of consecutive patients who were managed at our centre for FNH between January 1997 and December 2006 was performed.
RESULTS: The cohort was divided into two groups of patients: those who were managed surgically (n=15) and those managed conservatively (n=37). There was no correlation between tumour size and number of lesions with oral contraceptive use (p=0.07 and 0.90, respectively) and pregnancy (p=0.45 and 0.60, respectively). However, tumour size (p=0.006) and number of lesions (p=0.02) were associated with the occurrence of pain in these patients. Pain was the commonest symptom of patients (13/15) who were managed surgically. All patients underwent radiological imaging before diagnosis. The sensitivities of ultrasound, CT scanning and MRI scanning in characterizing these lesions were 30%, 70% and 87%, respectively. There were no postoperative deaths and three postoperative complications that were successfully managed non-operatively. With a median follow-up of 24 months in the surgically treated group, one patient has developed recurrent symptoms of pain. CONCLUSION. In this series, there was no mortality directly due to the surgical procedure and a modest morbidity, justifying surgical resections in selected patients.

PMID: 18345321 [PubMed]
Hepatic resection for metastatic gastrointestinal and pancreatic neuroendocrine tumours: outcome and prognostic predictors.
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Hepatic resection for metastatic gastrointestinal and pancreatic neuroendocrine tumours: outcome and prognostic predictors.

HPB (Oxford). 2007;9(5):345-51

Authors: Gomez D, Malik HZ, Al-Mukthar A, Menon KV, Toogood GJ, Lodge JP, Prasad KR

Abstract
BACKGROUND: Treatment modalities for hepatic metastases from neuroendocrine tumours (NETs) include surgery, somatostatin analogues and arterial embolization. The aims of this study were to evaluate the outcome of patients following surgery and to identify prognostic predictors of recurrent disease.
PATIENTS AND METHODS: This was a retrospective clinico-pathological analysis of patients managed with hepatic NET metastases over a 13-year period (January 1994 to December 2006).
RESULTS: Eighteen patients with hepatic metastases from NET were identified with a median age of 53 years (range 31-75). The localization of the primary tumour was the terminal ileum (n=8), pancreas (n=7), appendix (n=2) or duodenum (n=1). Twelve patients had synchronous disease and six patients developed metachronous hepatic tumours over a median period of 20 months (range 6-144). Presenting symptoms included abdominal pain (n =13), recurrent diarrhoea (n=7) and flushing (n=7). Fifteen patients underwent surgery with complete cytoreduction and three patients had partial cytoreduction. The overall 2- and 5-year actuarial survival rates were 94% and 86%, respectively. The 2- and 5-year disease-free rates following hepatic resection with complete cytoreduction were both 66%. Partial or complete control of endocrine-related symptoms was achieved in all patients with functioning tumours following surgery. Recurrent disease occurred in four patients following complete cytoreductive surgery. Resection margin involvement was associated with developing recurrent disease (p=0.041).
CONCLUSION: Surgical resection for hepatic NET metastases results in good long-term survival in selected patients and resection margin involvement was associated with recurrent disease.

PMID: 18345317 [PubMed]
Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma.
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Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma.

World J Surg. 2008 Aug;32(8):1757-62

Authors: Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, Prasad KR

Abstract
BACKGROUND: This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC).
METHODS: Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed.
RESULTS: A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15-85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR >or=5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR >or= 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR >or= 5 was 8 months compared with 18 months for those with a NLR < 5.
CONCLUSION: Preoperative NLR >or= 5 was an adverse predictor of disease-free and overall survival.

PMID: 18340479 [PubMed - indexed for MEDLINE]
Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma.
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Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma.

J Surg Oncol. 2008 May 1;97(6):513-8

Authors: Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP, Prasad KR

Abstract
AIMS: To analyse the results and prognostic factors affecting disease-free and overall survival following potentially curative resection for intrahepatic cholangiocarcinoma (IHCC).
METHODS: Patients undergoing resection for IHCC from January 1996 to December 2006 were included. Data analysed included demographics, clinical and histopathology data.
RESULTS: Twenty-seven patients were identified with a median age of 57 (32-84) years. The 1-, 3- and 5-year overall and disease-free survival rates were 74%, 16% and 16%, and 44%, 15% and 15%, respectively. On univariate analysis, age <65 years, female gender, neutrophil to lymphocyte ratio (NLR) >or= 5, micro-vascular invasion and lymph node involvement were predictors of poorer overall survival. Multivariate analysis did not identify any independent predictors of overall survival. A NLR >or= 5 was the only adverse predictor of disease-free survival. The median disease-free survival of patients with NLR >or= 5 was 6 months compared to 18 months for those with NLR < 5. There was a significant association between patients with a NLR >or= 5 and larger tumour size, satellite lesions, micro-vascular invasion and lymph node involvement.
CONCLUSION: Long-term outcome following resection of IHCC is poor. A pre-operative NLR >or= 5 was an adverse predictor of disease-free survival and was associated with an aggressive tumour biology profile.

PMID: 18335453 [PubMed - indexed for MEDLINE]
Mirizzi's syndrome--results from a large western experience.
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Mirizzi's syndrome--results from a large western experience.

HPB (Oxford). 2006;8(6):474-9

Authors: Gomez D, Rahman SH, Toogood GJ, Prasad KR, Lodge JP, Guillou PJ, Menon KV

Abstract
BACKGROUND: This paper reports a series of patients with Mirizzi's syndrome (MS) who were managed at our institution over an 11-year (1994-2005) period.
METHODS: Retrospective case note study of patients with a definitive or possible diagnosis of MS stated in radiology reports were identified using the hospital's radiology computer coding system.
RESULTS: 33 patients were identified with a median age of diagnosis of 70 (35-90) years and male to female ratio of 15:18. Liver function tests were deranged in all patients. Pre-operative radiological diagnosis was achieved in 28 patients: ultrasound scan (n = 4), computer tomography (n = 3), magnetic resonance cholangiopancreatography (n = 10) and endoscopic retrograde cholangiopancreatography (n = 11). Five patients were diagnosed intra-operatively. Type I MS was reported in 27 patients. Laparoscopic cholecystectomy was attempted in 18 patients with 6 being converted to open cholecystectomy. Six patients had biliary stent insertion only and 3 were conservatively managed. Six patients had type II MS, 4 were treated with open cholecystectomy and Roux-en-Y hepaticojejunostomy, 1 underwent an open subtotal cholecystectomy with fistula closure and 1 had percutaneous biliary stent insertion only. The median follow-up period was 2 (1-7) months (n = 18). 10 patients are currently under follow-up. Overall morbidity was 27% (n = 8) and mortality was 7% (n = 2).
CONCLUSION: Pre-operative diagnosis of MS can be achieved using MRCP. Laparoscopic cholecystectomy for type I MS is a safe option and type II MS can be treated with Roux-en-Y hepaticojejunostomy or subtotal cholecystectomy with fistula closure.

PMID: 18333104 [PubMed]
Non-operative management of pyogenic liver abscess.
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Non-operative management of pyogenic liver abscess.

HPB (Oxford). 2003;5(2):91-5

Authors: Pearce NW, Knight R, Irving H, Menon K, Prasad KR, Pollard SG, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Liver abscess is a serious disease traditionally managed by open drainage. The advances in interventional radiology over the last two decades have allowed a change in approach to this condition. We have reviewed our experience in managing liver abscess over the last 7 years.
METHODS: Details of all patients admitted with liver abscess between 1995 and 2002 were prospectively entered onto our database. A review was performed to document the use of imaging and drainage techniques. Aetiology, morbidity, mortality and duration of hospital stay were recorded.
RESULTS: Forty-two patients (median age 53 [22-85] years; M:F 18:24) were admitted with liver abscess (multiple abscess 20); 19 cases were of portal tract origin, 16 cases were of biliary tract origin and 7 cases were spontaneous. Forty-one patients were managed non-operatively, all received antibiotics (cephalosporins 76%, metronidazole 88%, quinolones 33%). Diagnosis was made on ultrasound scan (22) or CT (20). Five patients were managed with antibiotics alone. Fifteen patients were managed initially with percutaneous aspiration and five subsequently required percutaneous drainage. Twenty-one patients had primary percutaneous drainage, nine requiring a further procedure (aspiration 3, drainage 6). One patient underwent hepatic resection. Median hospital stay was 16 (6-35) days. There was one death, but no procedure-related morbidity.
DISCUSSION: Non-operative management of solitary and multiple liver abscesses is safe and effective.

PMID: 18332963 [PubMed]
Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success.
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Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success.

Ann Surg. 2008 Feb;247(2):238-49

Authors: Lodge JP, Dasgupta D, Prasad KR, Attia M, Toogood GJ, Davies M, Millson C, Breslin N, Wyatt J, Robinson PJ, Bellamy MC, Snook N, Pollard SG

Abstract
INTRODUCTION: Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling King's College criteria for "super-urgent" liver transplantation.
METHODS: Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire.
RESULTS: Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0-102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients.
CONCLUSION: Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.

PMID: 18216528 [PubMed - indexed for MEDLINE]
Total laparoscopic pancreaticoduodenectomy and reconstruction for a cholangiocarcinoma of the bile duct.
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Total laparoscopic pancreaticoduodenectomy and reconstruction for a cholangiocarcinoma of the bile duct.

J Laparoendosc Adv Surg Tech A. 2007 Dec;17(6):775-80

Authors: Menon KV, Hayden JD, Prasad KR, Verbeke CS

Abstract
BACKGROUND: In this paper, we report on our experience with a totally laparoscopic pancreatico-duodenectomy performed for a cholangiocarcinoma of the lower third of the bile duct.
METHODS: The patient was placed in the steep reverse Trendelenberg, Lloyd-Davis position. The procedure was performed with six laparoscopic ports, using similar steps to the open approach, with the use of an ultrasonic cutting and coagulating instrument for dissection and endoscopic linear stapling devices for the bile duct, intestinal, and gastroduodenal artery division. Reconstruction was done on a single loop by an intracorporeally sutured pancreaticojejunostomy, hepaticojejunostomy, and a stapled gastroenterostomy. The resection specimen was placed in a bag and retrieved through a 5-cm Pfannenstiel incision.
RESULTS: Histology confirmed a T3 N1 R0 cholangiocarcinoma with the involvement of 1 of 17 lymph nodes. Twelve months following surgery, he remains well, having completed a course of adjuvant chemotherapy.
CONCLUSIONS: Although the operation was technically demanding, it can be safely performed with a good oncologic result.

PMID: 18158808 [PubMed - indexed for MEDLINE]
Right hepatic trisectionectomy for hepatobiliary diseases: results and an appraisal of its current role.
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Right hepatic trisectionectomy for hepatobiliary diseases: results and an appraisal of its current role.

Ann Surg. 2007 Dec;246(6):1065-74

Authors: Halazun KJ, Al-Mukhtar A, Aldouri A, Malik HZ, Attia MS, Prasad KR, Toogood GJ, Lodge JP

Abstract
OBJECTIVE: To assess the results of 275 patients undergoing right hepatic trisectionectomy and to clarify its current role.
SUMMARY BACKGROUND DATA: Right hepatic trisectionectomy is considered one of the most extensive liver resections, and few reports have described the long-term results of the procedure.
METHODS: Short- and long-term outcomes of 275 consecutive patients who underwent right hepatic trisectionectomy from January 1993 to January 2006 were analyzed.
RESULTS: Of the 275 patients, 160 had colorectal metastases, 49 had biliary tract cancers, 20 had hepatocellular carcinomas, 20 had other metastatic tumors, and 12 had benign diseases. Fourteen of the 275 patients underwent right hepatic trisectionectomy as part of auxiliary liver transplantation for acute liver failure and were excluded. Concomitant procedures were carried out in 192 patients: caudate lobectomy in 45 patients, resection of tumors from the liver remnant in 57 patients, resection of the extrahepatic biliary tree in 45 patients, and lymphadenectomy in 45 patients. One-, 3-, 5-, and 10-year survivals were 74%, 54%, 43%, and 36%, respectively. Overall hospital morbidity and 30-day and in-hospital mortalities were 41%, 7%, and 8%, respectively. Survivals for individual tumor types were acceptable, with 5-year survivals for colorectal metastasis and cholangiocarcinoma being 38% and 32%, respectively. Multivariate analysis disclosed the amount of intraoperative blood transfusion to be the sole independent predictor for the development of hospital morbidity. Age over 70 years, preoperative bilirubin levels, and the development of postoperative renal failure were found to be independent predictors of long-term survival.
CONCLUSION: Right hepatic trisectionectomy remains a challenging procedure. The outcome is not influenced by additional concomitant resection of tumors from the planned liver remnant. Caution must be taken when considering patients older than 70 years for such resections.

PMID: 18043112 [PubMed - indexed for MEDLINE]
Surgery for hilar cholangiocarcinoma: the Leeds experience.
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Surgery for hilar cholangiocarcinoma: the Leeds experience.

Eur J Surg Oncol. 2008 Jul;34(7):787-94

Authors: Hidalgo E, Asthana S, Nishio H, Wyatt J, Toogood GJ, Prasad KR, Lodge JP

Abstract
AIM: To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre.
METHODS: A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration.
RESULTS: Tumours were staged as follows (UICC 6th edition): stage IB, n=10 IIA, n=9; IIB, n=20; III, n=8; IV, n=14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n=3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p=0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p=0.0034, 95% confidence interval 0.1007-6.342).
CONCLUSIONS: Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.

PMID: 18036765 [PubMed - indexed for MEDLINE]
Surgeon's awareness of the synchronous liver metastases during colorectal cancer resection may affect outcome.
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Surgeon's awareness of the synchronous liver metastases during colorectal cancer resection may affect outcome.

Eur J Surg Oncol. 2008 Feb;34(2):180-4

Authors: Hamady ZZ, Malik HZ, Alwan N, Wyatt JI, Prasad KR, Prasad RK, Toogood GJ, Toogood GT, Lodge JP

Abstract
AIM: There is conflicting evidence about the importance of synchronous metastases upon tumor outcome. The aim of this study is to identify the effect of finding synchronous colorectal liver metastases on the performance of the surgeon whilst operating on primary colorectal cancer.
METHODS: Patients with completed colorectal cancer data who underwent liver resection for colorectal metastases between 1993 and 2001 were included. Two hundred seventy patients were categorised according to the site of the primary tumour (colon or rectum) and knowledge of the presence of liver metastases by the colorectal surgeon (SA=surgeon aware, n=112, SNA=surgeon not aware, n=158). The number of retrieved lymph nodes and colorectal resection margin involvement were used as surgical performance indicators. Survival and local recurrence rate were monitored.
RESULTS: The SA group had a higher rate of colorectal circumferential resection margin involvement, the local and intra-abdominal recurrence rate was also significantly higher in this group (p<0.001).
CONCLUSIONS: Awareness of the presence of liver metastases by the operating surgeon is an independent predictor of intra abdominal extra hepatic recurrence of colorectal cancer following potentially curative hepatic resection. This is related to an increased rate of primary colorectal resection margin involvement.

PMID: 17983724 [PubMed - indexed for MEDLINE]
Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases.
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Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases.

Ann Surg. 2007 Nov;246(5):806-14

Authors: Malik HZ, Prasad KR, Halazun KJ, Aldoori A, Al-Mukhtar A, Gomez D, Lodge JP, Toogood GJ

Abstract
BACKGROUND: Despite indications for resection of colorectal liver metastases having expanded, debate continues about identifying patients that may benefit from surgery.
METHODS: Clinicopathologic data from a total of 700 patients was gathered between January 1993 and January 2006 from a prospectively maintained dataset. Of these, 687 patients underwent resection for colorectal liver metastases.
RESULTS: The median age of patient was 64 years and 36.8% of patients had synchronous disease. The overall 5-year survival was 45%. The presence of an inflammatory response to tumor (IRT), defined by an elevated C-reactive protein (>10 mg/L) or a neutrophil/lymphocyte ratio of >5:1, was noted in 24.5% of cases. Only the number of metastases and the presence or absence of an IRT influenced both overall and disease-free survival on multivariable analysis. A preoperative prognostic score was derived: 0 = less than 8 metastases and absence of IRT; 1 = 8 or more metastases or IRT, and 2 = 8 or more metastases and IRT-from the results of the multivariable analysis. The 5-year survival of those scoring 0 was 49% compared with 34% for those scoring 1. None of the patients that scored 2 were alive at 5 years.
CONCLUSION: The preoperative prognostic score is a simple and effective system allowing preoperative stratification.

PMID: 17968173 [PubMed - indexed for MEDLINE]
Calcium carbonate gallstones in children.
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Calcium carbonate gallstones in children.

J Pediatr Surg. 2007 Oct;42(10):1677-82

Authors: Stringer MD, Soloway RD, Taylor DR, Riyad K, Toogood G

Abstract
BACKGROUND: In the United States, cholesterol stones account for 70% to 95% of adult gallstones and black pigment stones for most of the remainder. Calcium carbonate stones are exceptionally rare. A previous analysis of a small number of pediatric gallstones from the north of England showed a remarkably high prevalence of calcium carbonate stones. The aims of this study were to analyze a much larger series of pediatric gallstones from our region and to compare their chemical composition with a series of adult gallstones from the same geographic area.
METHODS: A consecutive series of gallbladder stones from 63 children and 50 adults from the north of England were analyzed in detail using Fourier transform infrared microspectroscopy. Demographic and clinical data were collected on all patients. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, calcium carbonate, and hydroxyapatite.
RESULTS: Thirty-nine (78%) adults had typical cholesterol stones, 7 (14%) had black pigment bilirubinate stones, and only 2 (4%) had calcium carbonate stones. In contrast, 30 (48%) children had black pigment stones, 13 (21%) had cholesterol stones, 15 (24%) had calcium carbonate stones, 3 (5%) had protein dominant stones, and 2 (3%) had brown pigment stones. In children, cholesterol stones were more likely in overweight adolescent girls with a family history of gallstones, whereas black pigment stones were equally common in boys and girls and associated with hemolysis, parenteral nutrition, and neonatal abdominal surgery. Calcium carbonate stones were more common in boys, and almost half had undergone neonatal abdominal surgery and/or required neonatal intensive care.
CONCLUSION: The composition of pediatric gallstones differs significantly from that found in adults. In particular, one quarter of the children in this series had calcium carbonate stones, previously considered rare. Geographic differences are not the major reason for the high prevalence of calcium carbonate gallstones in children.

PMID: 17923195 [PubMed - indexed for MEDLINE]