157 results on '"Toogood GJ"'
Search Results
2. Variation in the Use of Resection for Colorectal Cancer Liver Metastases
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Fenton, HM, Taylor, JC, Lodge, JPA, Toogood, GJ, Finan, PJ, Young, AL, and Morris, EJA
- Abstract
Objective: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS. Background: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist. Methods: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified. Result: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%–12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10–1.35) than those treated in one without. This effect was absent in resection for metachronous metastases. Conclusions: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.
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- 2019
3. Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases
- Author
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Watson, H, Cockbain, AJ, Spencer, J, Race, A, Volpato, M, Loadman, PM, Toogood, GJ, and Hull, MA
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lipids (amino acids, peptides, and proteins) ,social sciences ,complex mixtures ,geographic locations ,health care economics and organizations - Abstract
We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014). There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26 [±0.14]% increase; P
- Published
- 2016
4. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial
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Nordlinger, B, Sorbye, H, Glimelius, B, Poston, Gj, Schlag, Pm, Rougier, P, Bechstein, Wo, Primrose, Jn, Walpole, Et, FINCH JONES, M, Jaeck, D, Mirza, D, Parks, Rw, Collette, L, Praet, M, Bethe, U, VAN CUTSEM, E, Scheithauer, W, Gruenberger, T, Hohenberger, W, Iveson, T, Karner, J, Levi, J, Hugh, T, DE GREVE, J, Chan, A, Davidson, B, Lindner, P, Peeters, M, Stein, B, Diamond, T, Ducreux, M, Lasser, P, Graeven, U, Paillot, B, Doran, J, Gouillat, C, Iesalnieks, I, Jauch, Kw, JAGOT LACOUSSIERE, P, Jansen, Rl, Koehne, H, Konopke, R, Otto, F, Sherlock, D, VAN HAZEL, G, Ackland, S, Bedenne, L, Bories, E, CLAVERO FABRI MC, Conroy, T, KAMINSKY FORRETT MC, Husseini, F, Karapetis, C, Mãœller, L, Price, T, Rosenberg, R, Schott, J, Tschmelitsch, J, VAN LAETHEM JL, Wals, J, Weimann, A, Arnaud, Jp, Arsene, D, Auby, D, Bhattacharya, S, Cebon, E, Cherqui, D, Confente, C, Dousset, B, Frickhofen, N, Frilling, A, Evan, P, Ganju, V, Hã–ffken, K, Lazorthes, F, Letoublon, C, Madroszyk, A, Nitti, Donato, Orr, B, Pariente, Ea, Pector, Jc, Raoul, Jl, Rees, M, Ridwelski, K, Rouanet, P, Toogood, Gj, Vergauwe, P, Wilke, Hj, Kaplan, R, Horiot, Jc, Littbrand, B, Awada, A, Stenning, S, Lejeune, F., Haukeland University Hospital, University of Bergen (UiB), Uppsala Universitet [Uppsala], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Chirurgie Viscérale, Hépatique et de Transplantation Multiorganes, Université Louis Pasteur - Strasbourg I, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), University Hospitals Leuven [Leuven], Centre Énergétique et Procédés (CEP), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
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Adult ,Male ,medicine.medical_specialty ,Organoplatinum Compounds ,Colorectal cancer ,[SDV]Life Sciences [q-bio] ,030230 surgery ,Perioperative Care ,03 medical and health sciences ,0302 clinical medicine ,Hepatic arterial infusion ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,business.industry ,Liver Neoplasms ,Hazard ratio ,Cancer ,General Medicine ,Perioperative ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,3. Good health ,Surgery ,Oxaliplatin ,Clinical trial ,030220 oncology & carcinogenesis ,Female ,Fluorouracil ,Colorectal Neoplasms ,Liver cancer ,business ,medicine.drug - Abstract
Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
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- 2008
5. Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases
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Young, AL, Chalmers, CR, Hawcroft, G, Perry, SL, Treanor, D, Toogood, GJ, Jones, PF, and 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.
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- 2013
6. Biliary and portal vein strictures following treatment of Hodgkin’s lymphoma
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Roberts, KJ, primary, Brown, R, additional, Patel, JV, additional, and Toogood, GJ, additional
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- 2012
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7. Performance and Quality Indicators: The Importance of Accurate Coding
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Cockbain, AJ, primary, Carolan, M, additional, Berridge, D, additional, and Toogood, GJ, additional
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- 2012
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8. Acute Laparoscopic Cholecystectomy: Delays in Acute Surgery and Cost Analysis of Aproposed New Service
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Cockbain, AJ, primary, Young, AL, additional, McGinnes, E, additional, and Toogood, GJ, additional
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- 2011
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9. Hepatobiliary and Pancreatic: Agenesis of the gallbladder
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Cockbain, AJ, primary, Watson, J, additional, and Toogood, GJ, additional
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- 2011
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10. Salvage transplantation for stage IVa hepatocellular carcinoma, what are the guidelines?
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Goldsmith, PJ, primary, Toogood, GJ, additional, Lodge, JPA, additional, and Prasad, KR, additional
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- 2009
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11. Cyclooxygenase-2 protein expression in colorectal cancer liver metastases
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Chapple, Ks, primary, Fenwick, Sw, additional, Toogood, Gj, additional, Lodge, Jpa, additional, and Hull, Ma, additional
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- 2000
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12. Preoperative determinants of common bile duct stones during laparoscopic cholecystectomy.
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Sheen AJ, Asthana S, Al-Mukhtar A, Attia M, and Toogood GJ
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Introduction: The aim of this study is to determine whether there are any clinical or biochemical predictors of common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy. Methods: A prospective database of nearly 1000 laparoscopic cholecystectomies performed under the care of a single surgeon with a standardised technique between 1999 and 2006, was analysed. Clinical presentation, ultrasound and immediate preoperative biochemical results as well as the operative cholangiogram findings were reviewed. Routine cholangiography was attempted in most patients and the primary outcome variable was the detection of bile duct stones. The data was analysed using chi-squared test for categorical variables. The significant variables on univariate analysis were further characterised to identify the independent predictors of bile duct stones using a logistic regression model (significance p < 0.05). Results: A total of 757 of 988 patients (77%) underwent cholangiography. Male-to-female ratio was 1 : 3 with a median age of 54 years (range: 17-93). Ten per cent of patients had bile duct stones identified on cholangiography. On univariate analysis, jaundice (p = 0.019), cholangitis (p < 0.001), alanine transaminase > 100 (p = 0.024), alkaline phosphatase (ALP) > 350 (p < 0.001) and CBD > 10 mm (p = 0.01) were significant markers for predicting bile duct stones. Bilirubin > 30 (x2 normal) was found not to be significant (p = 0.145). On a logistic regression model, ALP > 350 and/or cholangitis were found to be independent predictive factors of CBD stones (odds ratio 6.1). Conclusions: If a policy of routine intra-operative cholangiography is not adopted, a history of cholangitis or a raised ALP immediately preoperatively should lead to a high suspicion of CBD stones. [ABSTRACT FROM AUTHOR]
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- 2008
13. Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: surgical approaches and outcomes.
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Young AL, Adair R, Prasad KR, Toogood GJ, and Lodge JP
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- 2012
14. Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n -3 PUFA levels: an analysis of the UK Biobank.
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Aldoori J, Zulyniak MA, Toogood GJ, and Hull MA
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- Humans, United Kingdom, Male, Female, Middle Aged, Aged, Diet, Adult, Biological Specimen Banks, Seafood, Animals, UK Biobank, Fish Oils administration & dosage, Fatty Acids, Omega-3 blood, Fatty Acids, Omega-3 administration & dosage, Dietary Supplements, Fishes
- Abstract
Observational evidence linking dietary n -3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n -3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n -3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n -3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use ( P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n -3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n -3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n -3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n -3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n -3 PUFA intake, blood levels of n -3 PUFAs and health outcomes.
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- 2024
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15. Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.
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Hull MA, Ow PL, Ruddock S, Brend T, Smith AF, Marshall H, Song M, Chan AT, Garrett WS, Yilmaz O, Drew DA, Collinson F, Cockbain AJ, Jones R, Loadman PM, Hall PS, Moriarty C, Cairns DA, and Toogood GJ
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- Humans, Eicosapentaenoic Acid therapeutic use, Quality of Life, Treatment Outcome, Neoplasm Recurrence, Local drug therapy, Double-Blind Method, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Colorectal Neoplasms pathology, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Liver Neoplasms secondary
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Introduction: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis., Methods and Analysis: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%., Ethics and Dissemination: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently., Trial Registration Number: NCT03428477., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
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- 2023
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16. Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.
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Samson A, West EJ, Carmichael J, Scott KJ, Turnbull S, Kuszlewicz B, Dave RV, Peckham-Cooper A, Tidswell E, Kingston J, Johnpulle M, da Silva B, Jennings VA, Bendjama K, Stojkowitz N, Lusky M, Prasad KR, Toogood GJ, Auer R, Bell J, Twelves CJ, Harrington KJ, Vile RG, Pandha H, Errington-Mais F, Ralph C, Newton DJ, Anthoney A, Melcher AA, and Collinson F
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- Humans, Leukocytes, Mononuclear, Neoadjuvant Therapy, Vaccinia virus genetics, Liver Neoplasms therapy, Oncolytic Virotherapy methods, Oncolytic Viruses genetics
- Abstract
Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2022
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17. A multi-center post-market clinical study to confirm safety and performance of PuraStat® in the management of bleeding during open liver resection.
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Nahm CB, Popescu I, Botea F, Fenwick S, Fondevila C, Bilbao I, Reim D, and Toogood GJ
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- Adolescent, Hemorrhage etiology, Hepatectomy adverse effects, Humans, Liver, Prospective Studies, Hemostatics adverse effects
- Abstract
Background: PuraStat® is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat® in liver resections performed for metastatic tumors., Methods: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were ≥18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat® for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use., Results: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat® application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified., Conclusion: This study confirms the safety, efficacy and ease of use of PuraStat® in the management of bleeding in liver surgery., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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18. Omega-3 polyunsaturated fatty acids: moving towards precision use for prevention and treatment of colorectal cancer.
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Aldoori J, Cockbain AJ, Toogood GJ, and Hull MA
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- Humans, Microsatellite Instability, Prospective Studies, Adenoma pathology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms prevention & control, Fatty Acids, Omega-3 therapeutic use
- Abstract
Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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19. Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.
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Nana G, Mitra S, Watson H, Young C, Wood HM, Perry SL, Race AD, Quirke P, Toogood GJ, Loadman PM, and Hull MA
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- Biological Availability, Humans, Ileum, Middle Aged, RNA, Ribosomal, 16S genetics, Gastrointestinal Microbiome, Ileostomy
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Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut., Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum., Methods: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC-tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing., Results: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05)., Conclusions: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
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- 2021
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20. COVID-19 research priorities in surgery (PRODUCE study): A modified Delphi process.
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Allan M, Mahawar K, Blackwell S, Catena F, Chand M, Dames N, Goel R, Graham YN, Kothari SN, Laidlaw L, Mayol J, Moug S, Petersen RP, Pryor AD, Smart NJ, Taylor M, Toogood GJ, Wexner SD, Zevin B, and Wilson MS
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- Delphi Technique, Humans, Surveys and Questionnaires, COVID-19 epidemiology, General Surgery organization & administration, Health Priorities organization & administration, Pandemics, Research organization & administration, SARS-CoV-2, Societies, Medical
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- 2020
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21. Outcomes of liver resection for hepatocellular carcinoma in octogenarians.
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Sanyal S, Kron P, Wylie N, Hildalgo E, Toogood GJ, and Lodge P
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- Aged, 80 and over, Hepatectomy adverse effects, Humans, Retrospective Studies, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery
- Abstract
Background: There is a dearth of information about operative outcomes in patients ≥80 years for hepatocellular carcinoma (HCC) from Western institutions. We compare the result of HCC resections in patients <80 years vs. patients ≥80 years from our institution in the UK., Methods: We conducted a retrospective review of all patients undergoing liver resections for HCC between 2005 and 2015. Demographics, comorbidities, morbidity, mortality and survival were compared between the two age groups., Results: 200 patients underwent resection for HCC in this time period. Nineteen patients were ≥80 years and 181 were <80 years. Comorbidities measured by the Charlson Comorbidity Index were significantly higher in the ≥80 group (p < 0.0001). There was no significant difference in the extent of resection in the two groups. Morbidity and mortality between the <80 years and the ≥80 years group were not significantly different (morbidity 27% vs.16%; p = 0.29) (mortality 7% vs. 0%; p = 0.11). The one-year (83.4% vs. 88.2%; p = 0.83), five-year (56.3% vs. 55.8%; p = 0.83) and the overall survival rate rates (887 days vs. 1035 days; p = 0.66) were not significantly different between the groups., Discussion: Liver resection should not be precluded based on age alone; with good outcomes in patients ≥80 years justifying surgery., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)
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- 2020
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22. Variation in the Use of Resection for Colorectal Cancer Liver Metastases.
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Fenton HM, Taylor JC, Lodge JPA, Toogood GJ, Finan PJ, Young AL, and Morris EJA
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- Adult, Aged, Cohort Studies, Colectomy methods, Disease-Free Survival, Female, Hepatectomy statistics & numerical data, Humans, Incidence, Kaplan-Meier Estimate, Liver Neoplasms mortality, Logistic Models, Male, Middle Aged, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Assessment, Survival Analysis, United Kingdom, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, Hepatectomy methods, Liver Neoplasms secondary, Liver Neoplasms surgery, Registries
- Abstract
Objective: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS., Background: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist., Methods: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified., Result: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%-12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10-1.35) than those treated in one without. This effect was absent in resection for metachronous metastases., Conclusions: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.
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- 2019
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23. Ablation or Resection for Colorectal Liver Metastases? A Systematic Review of the Literature.
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Kron P, Linecker M, Jones RP, Toogood GJ, Clavien PA, and Lodge JPA
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Background: Successful use of ablation for small hepatocellular carcinomas (HCC) has led to interest in the role of ablation for colorectal liver metastases (CRLM). However, there remains a lack of clarity about the use of ablation for colorectal liver metastases (CRLM), specifically its efficacy compared with hepatic resection. Methods: A systematic review of the literature on ablation or resection of colorectal liver metastases was performed using MEDLINE, Cochrane Library, and Embase until December 2018. The aim of this study was to summarize the evidence for ablation vs. resection in the treatment of CRLM. Results: This review identified 1,773 studies of which 18 were eligible for inclusion. In the majority of the studies, overall survival (OS) and disease-free survival (DFS) were significantly higher and local recurrence (LR) rates were significantly lower in the resection groups. On subgroup analysis of solitary CRLM, resection was associated with improved OS, DFS, and reduced LR. Three series assessed the outcome of resection vs. ablation for technically resectable CRLM, and showed improved outcome in the resection group. In fact, there were no studies showing a survival advantage of ablation compared to resection in the treatment of CRLM. Conclusions: Resection remains the "gold standard" in the treatment of CRLM and should not be replaced by ablation at present. This review supports the use of ablation only as an adjunct to resection and as a single treatment option when resection is not safely possible., (Copyright © 2019 Kron, Linecker, Jones, Toogood, Clavien and Lodge.)
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- 2019
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24. Segment 2/3 Hypertrophy is Greater When Right Portal Vein Embolisation is Extended to Segment 4 in Patients with Colorectal Liver Metastases: A Retrospective Cohort Study.
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Hammond CJ, Ali S, Haq H, Luo L, Wyatt JI, Toogood GJ, Lodge JPA, and Patel JV
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- Aged, Cohort Studies, Female, Humans, Hypertrophy, Liver pathology, Liver Neoplasms pathology, Male, Retrospective Studies, Treatment Outcome, Colorectal Neoplasms pathology, Embolization, Therapeutic methods, Liver Neoplasms secondary, Liver Neoplasms therapy, Portal Vein
- Abstract
Background: In patients with colorectal cancer liver metastases (CRLM), right portal vein embolisation (RPVE) is used to increase the volume of the future remnant liver (FRL) before major hepatic resection. It is not established whether embolisation of segment 4 in addition RPVE (RPVE + 4) induces greater hypertrophy of the FRL. Limitations of prior studies include heterogenous populations and use of hypertrophy metrics sensitive to baseline variables., Methods: From 2010 to 2015, consecutive patients undergoing RPVE or RPVE + 4 for CRLM, who had not undergone prior major hepatic resection and in whom imaging was available, were included in a retrospective study. Data were extracted from hospital electronic records. Volumetric assessments of segments 2-3 were made on cross-sectional imaging before and after embolisation and corrected for standardised liver volume., Results: Ninety-nine patients underwent PVE, and 60 met the inclusion criteria. Thirty-eight patients underwent RPVE, and 22 underwent RPVE + 4. Forty-five patients had undergone median 6 cycles of prior chemotherapy. Eighteen patients had FRL metastases at PVE, and 16 had undergone subsegmental metastasectomy in the FRL. Assessments of the degree of hypertrophy (DH) of segments 2/3 were made at median 35 (interquartile range 30-49) days after PVE. RPVE + 4 resulted in a significantly greater increase in DH than RPVE (7.7 ± 1.8% vs 11.3 ± 2.6%, p = 0.011). No confounding association between baseline variables and the decision to undertake RPVE or RPVE + 4 was identified. Median survival was 2.4 years and was not influenced by segment 4 embolisation., Conclusion: RPVE + 4 results in greater DH of segments 2/3 than RPVE in people with CLRM.
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- 2019
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25. A Randomized Controlled Trial Comparing Epidural Analgesia Versus Continuous Local Anesthetic Infiltration Via Abdominal Wound Catheter in Open Liver Resection.
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Bell R, Ward D, Jeffery J, Toogood GJ, Lodge JA, Rao K, Lotia S, and Hidalgo E
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- Abdomen, Adult, Aged, Aged, 80 and over, Catheterization methods, Female, Follow-Up Studies, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Pain, Postoperative diagnosis, Pain, Postoperative epidemiology, Prospective Studies, Recovery of Function, Surgical Wound, Treatment Outcome, Analgesia, Epidural, Analgesia, Patient-Controlled methods, Anesthesia, Local methods, Enhanced Recovery After Surgery, Hepatectomy methods, Pain, Postoperative prevention & control
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Aim: To compare outcomes following open liver resection (OLR) between patients receiving thoracic epidural (EP) versus abdominal wound catheters plus patient-controlled analgesia (AWC-PCA)., Method: Patients were randomized 1:1 to either EP or AWC-PCA within an enhanced recovery protocol. Primary outcome was length of stay (LOS), other variables included functional recovery, pain scores, peak flow, vasopressor and fluid requirements, and postoperative complications., Results: Between April 2015 and November 2017, 83 patients were randomized to EP (n = 41) or AWC-PCA (n = 42). Baseline demographics were comparable. No difference was noted in LOS (EP 6 d (3-27) vs AWC-PCA 6 d (3-66), P = 0.886). Treatment failure was 20% in the EP group versus 7% in the AWC-PCA (P = 0.09). Preoperative anesthetic time was shorter in the AWC-PCA group, 49 minutes versus 62 minutes (P = 0.003). EP patients required more vasopressor support immediately postoperatively on day 0 (14% vs 54%, P = <0.001) and day 1 (5% vs 23%, P = 0.021). Pain scores were greater on day 0, afternoon of day 1 and morning of day 2 in the AWC-PCA group however were regarded as low at all time points. No other significant differences were noted in IV fluid requirements, nausea/sedation scores, days to open bowels, length of HDU, and postoperative complications., Conclusion: AWC-PCA was associated with reduced treatment failure and a reduced vasopressor requirement than EP up to 2 days postoperatively. While the use of AWC-PCA did not translate into a shorter LOS in this study, it simplified patient management after OLR. EP cannot be routinely recommended following open liver resections.
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- 2019
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26. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.
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Watson H, Mitra S, Croden FC, Taylor M, Wood HM, Perry SL, Spencer JA, Quirke P, Toogood GJ, Lawton CL, Dye L, Loadman PM, and Hull MA
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- Aged, Chromatography, Liquid, Cross-Over Studies, Dietary Supplements, Fatty Acids blood, Female, Healthy Volunteers, Humans, Male, Mass Spectrometry, Middle Aged, Polymerase Chain Reaction, Fatty Acids, Omega-3 therapeutic use, Feces microbiology, Gastrointestinal Microbiome drug effects
- Abstract
Objective: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22)., Design: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry., Results: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium , Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects., Conclusion: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure., Trial Registration Number: ISRCTN18662143., Competing Interests: Competing interests: MH acts as a consultant advisor for Thetis Pharmaceuticals., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
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- 2018
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27. Impact of blood transfusion on outcomes following resection for colorectal liver metastases in the modern era.
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Pathak S, Al-Duwaisan A, Khoyratty F, Lodge JPA, Toogood GJ, Salib E, Prasad KR, and Miskovic D
- Abstract
Background: Evidence suggests that perioperative blood loss and blood transfusions are associated with poorer long-term outcomes in patients undergoing other oncological surgery. The aim of this study was to determine the long-term outcomes of patients requiring a blood transfusion post-hepatectomy for colorectal liver metastases (CRLM)., Methods: This is a retrospective review from 2005 to 2012. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier curves. Red blood cell transfusion (RBCT) and other clinic-pathological parameters were handled as covariates for Cox regression analysis., Results: Six hundred and ninety patients were included. Median follow-up was 33 months. Sixty-four (9.3%) patients required a perioperative RBCT. RBCT was a predictor for decreased OS (median 41 versus 49 months, P = 0.04). However, on multivariate regression analyses preoperative chemotherapy, post-operative complications and Clinical Risk Score were independently associated with reduced OS, though RBCT was not. There was no association between RBCT and RFS (median 15 versus 17 months, P = 0.28)., Conclusions: RBCT is not independently associated with a poorer OS., (© 2018 Royal Australasian College of Surgeons.)
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- 2018
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28. Expectations of outcomes in patients with colorectal cancer.
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Young AL, Lee E, Absolom K, Baxter H, Christophi C, Lodge JPA, Glaser AG, and Toogood GJ
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Background: Understanding patients' expectations of their treatment is critical to ensure appropriate treatment decisions, and to explore how expectations influence coping, quality of life and well-being. This study aimed to examine these issues related to treatment in patients with colorectal cancer., Methods: A literature search from January 1946 to September 2016 was performed to identify available data regarding patients' expectations of outcomes following colorectal cancer treatment. A narrative synthesis of the evidence was planned., Results: Of 4337 items initially identified, 20 articles were included in the review. In studies presenting data on overall and short-term survival, patients considerably overestimated prognosis. Patients also had unrealistic expectations of the negative aspects of chemotherapy and stomas. There was marked discordance between patients' and clinicians' expectations regarding chemotherapy, end-of-life care, bowel function and psychosocial outcomes. Level of education was the most consistent factor influencing the accuracy of patients' expectations., Conclusion: Patients with colorectal cancer frequently have unrealistic expectations of treatment. Marked disparities exist between patients' and clinicians' expectations of outcomes.
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- 2018
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29. Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors.
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Kimura N, Young AL, Toyoki Y, Wyatt JI, Toogood GJ, Hidalgo E, Prasad KR, Kudo D, Ishido K, Hakamada K, and Lodge JPA
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- Adult, Age Factors, Aged, Bile Duct Neoplasms mortality, Cohort Studies, Disease-Free Survival, Female, Hepatectomy mortality, Hospitals, University, Humans, Japan, Kaplan-Meier Estimate, Klatskin Tumor mortality, Male, Middle Aged, Multivariate Analysis, Neoplasm Invasiveness pathology, Neoplasm Staging, Outcome Assessment, Health Care, Postoperative Complications mortality, Postoperative Complications physiopathology, Postoperative Complications surgery, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sex Factors, Survival Analysis, Treatment Outcome, United Kingdom, Bile Duct Neoplasms pathology, Bile Duct Neoplasms surgery, Hepatectomy methods, Klatskin Tumor pathology, Klatskin Tumor surgery
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Background: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience., Methods: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. James's University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared., Results: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90-day mortality (2.5% vs 13.6%, respectively), disease-specific 5-year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival., Conclusion: Disease-specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long-term survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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30. The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review.
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Young AL, Rowe IA, Absolom K, Jones RL, Downing A, Meader N, Glaser A, and Toogood GJ
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- Adaptation, Psychological, Anxiety epidemiology, Depression epidemiology, Humans, Caregivers psychology, Liver Transplantation, Quality of Life, Stress, Psychological epidemiology
- Abstract
Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health-Related Quality of Life (HRQL) of LT patients' main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers' needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients' family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2017
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31. A cost-effective analysis of fibrin sealants versus no sealant following open right hemihepatectomy for colorectal liver metastases.
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Pandanaboyana S, Bell R, Shah N, Lodge JPA, Hidalgo E, Toogood GJ, and Prasad KR
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- Adult, Aged, Aged, 80 and over, Blood Transfusion economics, Colorectal Neoplasms secondary, Cost-Benefit Analysis, Female, Fibrin Tissue Adhesive administration & dosage, Fibrin Tissue Adhesive therapeutic use, Humans, Length of Stay economics, Liver Neoplasms secondary, Male, Middle Aged, Perioperative Period, Postoperative Complications prevention & control, Postoperative Period, Prospective Studies, Colorectal Neoplasms surgery, Fibrin Tissue Adhesive economics, Hepatectomy methods, Liver surgery, Liver Neoplasms surgery
- 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., (© 2014 Royal Australasian College of Surgeons.)
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- 2017
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32. Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases.
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Watson H, Cockbain AJ, Spencer J, Race A, Volpato M, Loadman PM, Toogood GJ, and Hull MA
- Subjects
- Colorectal Neoplasms metabolism, Disease-Free Survival, Double Bind Interaction, Female, Humans, Liver Neoplasms metabolism, Liver Neoplasms secondary, Male, Prognosis, Treatment Outcome, Colorectal Neoplasms blood, Eicosapentaenoic Acid administration & dosage, Fatty Acids, Omega-3 blood, Liver Neoplasms blood
- Abstract
We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of 'contamination' in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16-0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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33. Relationship between primary colorectal tumour and location of colorectal liver metastases.
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Pathak S, Palkhi E, Dave R, White A, Pandanaboyana S, Prasad KR, Lodge JP, and Toogood GJ
- Subjects
- Adult, Colorectal Neoplasms surgery, Female, Follow-Up Studies, Humans, Liver Neoplasms diagnosis, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Metastasis, Prospective Studies, Colorectal Neoplasms pathology, Diagnostic Imaging methods, Hepatectomy, Liver diagnostic imaging, Liver Neoplasms secondary
- 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., (© 2014 Royal Australasian College of Surgeons.)
- Published
- 2016
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34. Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy.
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Farid SG, White A, Khan N, Toogood GJ, Prasad KR, and Lodge JP
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Follow-Up Studies, Humans, Incidence, Length of Stay trends, Male, Middle Aged, Retrospective Studies, Survival Rate trends, Treatment Outcome, United Kingdom epidemiology, Young Adult, Bile Duct Neoplasms surgery, Carcinoma, Hepatocellular surgery, Cholangiocarcinoma surgery, Hepatectomy methods, Liver Neoplasms surgery, Postoperative Complications epidemiology
- 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., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)
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- 2016
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35. Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections.
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Morris-Stiff G, Marangoni G, Hakeem A, Farida SG, Gomez D, Toogood GJ, Lodge JP, and Raj Prasad K
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- Aged, Colorectal Neoplasms pathology, Databases, Factual, Female, Hepatectomy mortality, Humans, Length of Stay, Liver Neoplasms secondary, Male, Middle Aged, Prospective Studies, Hepatectomy classification, Liver Neoplasms surgery
- 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"., (Copyright © 2015. Published by Elsevier Ltd.)
- Published
- 2016
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36. Venous Thromboembolism Prophylaxis in Liver Surgery.
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Aloia TA, Geerts WH, Clary BM, Day RW, Hemming AW, D'Albuquerque LC, Vollmer CM Jr, Vauthey JN, and Toogood GJ
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- Anticoagulants therapeutic use, Humans, Liver surgery, Risk Factors, Hepatectomy adverse effects, Venous Thromboembolism prevention & control
- Abstract
Background: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation., Methods: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers., Results: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients., Conclusions: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.
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- 2016
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37. Anaesthetic and pharmacological techniques to decrease blood loss in liver surgery: a systematic review.
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Pathak S, Hakeem A, Pike T, Toogood GJ, Simpson M, Prasad KR, and Miskovic D
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- Hepatectomy adverse effects, Humans, Perioperative Period, Randomized Controlled Trials as Topic, Blood Loss, Surgical prevention & control, Hepatectomy methods, Liver surgery
- 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., (© 2015 Royal Australasian College of Surgeons.)
- Published
- 2015
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38. Management of gallbladder dyskinesia: patient outcomes following positive ⁹⁹mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with cholecystokinin (CCK) provocation and laparoscopic cholecystectomy.
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Dave RV, Pathak S, Cockbain AJ, Lodge JP, Smith AM, Chowdhury FU, and Toogood GJ
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- Adolescent, Adult, Aged, Biliary Dyskinesia metabolism, Cholecystokinin metabolism, Female, Humans, Imino Acids, Male, Middle Aged, Patient Satisfaction, Radionuclide Imaging, Retrospective Studies, Technetium, Treatment Outcome, Young Adult, Biliary Dyskinesia diagnostic imaging, Biliary Dyskinesia surgery, Cholecystectomy, Laparoscopic methods
- Abstract
Aims: To evaluate clinical outcomes in patients with typical biliary pain, normal ultrasonic findings, and a positive (99m)technetium (Tc)-labelled hepatic iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK) provocation indicating gallbladder dyskinesia, as per Rome III criteria, undergoing laparoscopic cholecystectomy (LC)., Methods and Materials: Consecutive patients undergoing LC for gallbladder dyskinesia were identified retrospectively. They were followed up by telephone interview and review of the electronic case records to assess symptom resolution., Results: One hundred consecutive patients (median age 44; 80% female) with abnormal gallbladder ejection fraction (GB-EF <35%) were followed up for a median of 12 months (range 2-80 months). Following LC, 84% reported symptomatic improvement and 52% had no residual pain. Twelve percent had persisting preoperative-type pain of either unchanged or worsening severity. Neither pathological features of chronic cholecystitis (87% of 92 incidences when histology available) nor reproduction of pain on CCK injection were significantly predictive of symptom outcome or pain relief post-LC., Conclusion: In one of the largest outcome series of gallbladder dyskinesia patients in the UK with a positive provocation HIDA scintigraphy examination and LC, the present study shows that the test is a useful functional diagnostic tool in the management of patients with typical biliary pain and normal ultrasound, with favourable outcomes following surgery., (Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)
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- 2015
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39. Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo.
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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, and Cook GP
- Subjects
- Aged, Antigens, CD immunology, Antigens, Differentiation, T-Lymphocyte immunology, Female, Humans, Interferons immunology, Killer Cells, Natural pathology, Lectins, C-Type immunology, Male, Middle Aged, Immunity, Cellular, Killer Cells, Natural immunology, Neoplasms immunology, Neoplasms therapy, Oncolytic Virotherapy, Oncolytic Viruses immunology, Reoviridae immunology
- 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., (© 2014 British Society for Immunology.)
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- 2015
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40. Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.
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Roberts KJ, Sutton AJ, Prasad KR, Toogood GJ, and Lodge JP
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- Aged, Antineoplastic Combined Chemotherapy Protocols economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Humans, Liver Neoplasms secondary, Liver Neoplasms therapy, Male, Markov Chains, Metastasectomy economics, Middle Aged, Palliative Care economics, Prospective Studies, Quality-Adjusted Life Years, Survival Analysis, Treatment Outcome, Colorectal Neoplasms, Liver Neoplasms economics
- 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., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)
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- 2015
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41. Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.
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Dave RV, Pathak S, White AD, Hidalgo E, Prasad KR, Lodge JP, Milton R, and Toogood GJ
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- Chemotherapy, Adjuvant mortality, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms surgery, Lung Neoplasms mortality, Lung Neoplasms surgery, Male, Metastasectomy methods, Metastasectomy mortality, Middle Aged, Retrospective Studies, Treatment Outcome, Colorectal Neoplasms, Liver Neoplasms secondary, Lung Neoplasms secondary
- 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., (© 2014 BJS Society Ltd. Published by John Wiley & Sons, Ltd.)
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- 2015
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42. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid.
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Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, Loadman PM, Toogood GJ, and Hull MA
- Subjects
- Adult, Aged, Aged, 80 and over, Chromatography, Liquid, Double-Blind Method, Eicosapentaenoic Acid metabolism, Female, Humans, Immunohistochemistry, Liver Neoplasms blood supply, Liver Neoplasms mortality, Liver Neoplasms surgery, Male, Middle Aged, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Tandem Mass Spectrometry, Anticarcinogenic Agents therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Eicosapentaenoic Acid pharmacology, Liver Neoplasms secondary
- 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2014
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43. 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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Hakeem AR, Marangoni G, Chapman SJ, Young RS, Nair A, Hidalgo EL, Toogood GJ, Wyatt JI, Lodge PA, and Prasad KR
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- Adult, Aged, Aged, 80 and over, Bile Duct Neoplasms immunology, Bile Duct Neoplasms pathology, Cholangiocarcinoma immunology, Cholangiocarcinoma pathology, Female, Humans, Kaplan-Meier Estimate, Leukocyte Count, Lymphatic Metastasis, Lymphocytes pathology, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Neutrophils pathology, Prognosis, Treatment Outcome, Bile Duct Neoplasms surgery, Bile Ducts, Intrahepatic, Cholangiocarcinoma secondary, Cholangiocarcinoma surgery, Lymph Node Excision methods
- 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.
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- 2014
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44. Viral warfare! Front-line defence and arming the immune system against cancer using oncolytic vaccinia and other viruses.
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Dave RV, Jebar AH, Jennings VA, Adair RA, West EJ, Errington-Mais F, Toogood GJ, and Melcher AA
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- Humans, Neoplasms immunology, Cancer Vaccines therapeutic use, Immunity, Cellular, Neoplasms therapy, Oncolytic Viruses immunology, Vaccination methods
- Abstract
Background: Despite mankind's many achievements, we are yet to find a cure for cancer. We are now approaching a new era which recognises the promise of harnessing the immune system for anti-cancer therapy. Pathogens have been implicated for decades as potential anti-cancer agents, but implementation into clinical therapy has been plagued with significant drawbacks. Newer 'designer' agents have addressed some of these concerns, in particular, a new breed of oncolytic virus: JX-594, a genetically engineered pox virus, is showing promise., Objective: To review the current literature on the use of oncolytic viruses in the treatment of cancer; both by direct oncolysis and stimulation of the immune system. The review will provide a background and historical progression for the surgeon on tumour immunology, and the interplay between oncolytic viruses, immune cells, inflammation on tumourigenesis., Methods: A literature review was performed using the Medline database., Conclusions: Viral therapeutics hold promise as a novel treatment modality for the treatment of disseminated malignancy. It provides a multi-pronged attack against tumour burden; direct tumour cell lysis, exposure of tumour-associated antigens (TAA), induction of immune danger signals, and recognition by immune effector cells., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2014
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45. Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.
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Morris-Stiff G, White AD, Gomez D, Cameron IC, Farid S, Toogood GJ, Lodge JP, and Prasad KR
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Adjuvant, Databases, Factual, Drug Administration Schedule, Female, Hepatic Veno-Occlusive Disease chemically induced, Humans, Liver drug effects, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Liver Regeneration, Magnetic Resonance Imaging, Male, Middle Aged, Organoplatinum Compounds administration & dosage, Oxaliplatin, Prospective Studies, Retrospective Studies, Antineoplastic Agents adverse effects, Colorectal Neoplasms pathology, Focal Nodular Hyperplasia chemically induced, Hepatectomy, Liver pathology, Liver Neoplasms secondary, Liver Neoplasms therapy, Neoadjuvant Therapy methods, Organoplatinum Compounds adverse effects
- 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., (Copyright © 2013. Published by Elsevier Ltd.)
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- 2014
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46. Performance of prognostic scores in predicting long-term outcome following resection of colorectal liver metastases.
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Roberts KJ, White A, Cockbain A, Hodson J, Hidalgo E, Toogood GJ, and Lodge JP
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- Aged, Colorectal Neoplasms mortality, Disease-Free Survival, Female, Humans, Liver Neoplasms mortality, Lung Neoplasms secondary, Male, Middle Aged, Neoplasm Recurrence, Local surgery, Retrospective Studies, Survival Rate, Time Factors, Treatment Outcome, Colorectal Neoplasms pathology, Liver Neoplasms secondary, Liver Neoplasms surgery
- Abstract
Background: Ten-year survival appears to define cure following resection of colorectal liver metastases (CRLMs). Various scores exist to predict outcome at 5 years. This study applied several scores to a patient cohort with 10 years of actual follow-up to assess their performance beyond 5 years., Methods: The study included consecutive patients who underwent liver resection at a single institution between 1992 and 2001. The ability of eight prognostic scoring systems to predict disease-free (DFS) and disease-specific (DSS) survival was analysed using the C-statistic., Results: Among 286 patients, the 1-, 3-, 5- and 10-year actual DSS rates were 86.6, 58.3, 39.5 and 24.5 per cent respectively. Seventy patients underwent 105 further resections for recurrent disease, of which 84.8 per cent were within 5 years of follow-up. Analysis of C-statistics showed only one score--the Rees postoperative index--to be a significant predictor of DFS and DSS at all time points. The remaining scores performed less well, and regularly showed no significant improvement in predictive accuracy over what would be expected by chance alone. No score yielded a C-statistic in excess of 0.8 at any time point., Conclusion: Although available risk scores can predict DFS and DSS, none does so with sufficient discriminatory accuracy to identify all episodes of recurrent disease. A non-negligible proportion of patients develop recurrent disease beyond 5 years of follow-up and so surveillance beyond this point may be advantageous., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)
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- 2014
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47. Xanthogranulomatous cholecystitis: a European and global perspective.
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Hale MD, Roberts KJ, Hodson J, Scott N, Sheridan M, and Toogood GJ
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- Americas epidemiology, Asia epidemiology, Cholecystitis diagnosis, Cholecystitis therapy, Diagnostic Errors, Endosonography, Europe epidemiology, Female, Gallbladder Neoplasms diagnosis, Gallbladder Neoplasms therapy, Granuloma diagnosis, Granuloma therapy, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Retrospective Studies, Tomography, X-Ray Computed, Xanthomatosis diagnosis, Xanthomatosis therapy, Cholecystitis epidemiology, Gallbladder Neoplasms epidemiology, Granuloma epidemiology, Xanthomatosis epidemiology
- Abstract
Introduction: Xanthogranulomatous cholecystitis (XGC) is often mistaken for, and may predispose to, gallbladder carcinoma (GB Ca). This study reviews the worldwide variation of the incidence, investigations, management and outcome of patients with XGC., Methods: Data from 29 studies, cumulatively containing 1599 patients, were reviewed and results summarized by geographical region (Europe, India, Far East and Americas) with 95% confidence intervals (CIs) to present variability within regions. The main study outcomes were incidence, association with GB Ca and treatment of patients with XGC., Results: Overall, the incidence of XGC was 1.3-1.9%, with the exception of India where it was 8.8%. The incidence of GB Ca associated with XGC was lowest in European studies (3.3%) varying from 5.1-5.9% in the remaining regions. Confusion with or undiagnosed GB Ca led to 10.2% of patients receiving over or under treatment., Conclusions: XGC is a global disease and is associated with GB Ca. Characteristic pathological, radiological and clinical features are shared with GB Ca and contribute to considerable treatment inaccuracy. Tissue sampling by pre-operative endoscopic ultrasound or intra-operative frozen section is required to accurately diagnose gallbladder pathology and should be performed before any extensive resection is performed., (© 2013 International Hepato-Pancreato-Biliary Association.)
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- 2014
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48. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.
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Hamady ZZ, Lodge JP, Welsh FK, Toogood GJ, White A, John T, and Rees M
- Subjects
- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms pathology, Disease-Free Survival, Female, Follow-Up Studies, Humans, Liver Neoplasms diagnosis, Liver Neoplasms secondary, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local prevention & control, Prognosis, Propensity Score, Retrospective Studies, Risk Factors, Survival Rate trends, Treatment Outcome, United Kingdom epidemiology, Young Adult, Colorectal Neoplasms surgery, Hepatectomy methods, Liver Neoplasms surgery
- 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.
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- 2014
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49. Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.
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Ziff O, Rajput I, Adair R, Toogood GJ, Prasad KR, and Lodge JP
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- Adenocarcinoma mortality, Adult, Aged, Chemotherapy, Adjuvant, Colorectal Neoplasms mortality, England, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Magnetic Resonance Imaging, Male, Middle Aged, Neoadjuvant Therapy, Reoperation, Retrospective Studies, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Adenocarcinoma secondary, Adenocarcinoma surgery, Colorectal Neoplasms pathology, Hepatectomy adverse effects, Hepatectomy mortality, Liver Neoplasms secondary, Liver Neoplasms surgery, Metastasectomy adverse effects, Metastasectomy mortality
- 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., (© 2013 International Hepato-Pancreato-Biliary Association.)
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- 2014
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50. Variation in referral practice for patients with colorectal cancer liver metastases.
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Young AL, Adair R, Culverwell A, Guthrie JA, Botterill ID, Toogood GJ, Lodge JP, and Prasad KR
- Subjects
- Adult, Aged, Aged, 80 and over, England, Female, Humans, Liver Neoplasms diagnostic imaging, Liver Neoplasms secondary, Male, Middle Aged, Patient Care Team, Prospective Studies, Radiography, Referral and Consultation standards, Retrospective Studies, Colorectal Neoplasms, Liver Neoplasms surgery, Referral and Consultation statistics & numerical data
- Abstract
Background: Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons., Methods: Patients presenting with new CLM in a cancer network consisting of a tertiary centre and seven attached hospitals were studied prospectively over 12 months. Data were collected retrospectively for patients who did not have a complete data set. Outcomes for patients referred to the liver tertiary centre were collated. The radiology of tumours deemed inoperable by the local colorectal specialist teams was reviewed by specialist liver surgeons and radiologists., Results: In total, 631 patients with CLM were assessed. Prospective data were complete for 241 patients, and 64 (26.6 per cent) of these were referred to the specialist liver team for consideration of resection. No decision was documented for 16 patients (6.6 per cent). Of those not referred, 30 (18.6 per cent) were deemed unfit or refused and 131 (81.4 per cent) were thought inoperable. Referral rates varied between hospitals (13-43.6 per cent). Of 131 patients deemed fit but inoperable by the colorectal specialist teams, 38 (29.0 per cent) were deemed operable and 20 (15.3 per cent) had equivocal imaging when assessed retrospectively by liver specialists. In total, 142 of the 631 patients were referred to liver specialists for consideration of treatments, and 107 (75.4 per cent) treated with curative intent., Conclusion: A considerable number of patients with potentially resectable CLM are not assessed by specialist liver teams. Improved referral rates could greatly improve resection rates for CLM, which may improve outcomes for patients with colorectal cancer., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
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