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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.

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.

Clinical outcomes for elderly patients undergoing liver resection for colorectal cancer (CRC) liver metastases are poorly characterised. This study aimed to investigate the impact of advancing age on the incidence of liver resection and post-operative outcomes.Patients in the National Bowel Cancer Audit undergoing major CRC resection from 2010 to 2016 in England were included. Liver resection was identified from linked Hospital Episode Statistics data. A Cox-proportional hazards model was used to compare 3-year mortality.Of 117,005 patients, 6081 underwent liver resection. For patients65 years there was 1 liver resection per 12 cases, 65-74, 1 per 17, and ≥75, 1 per 40. 90-day mortality after liver resection increased with advancing age (65 0.9% (26/2829), 65-74 2.8% (57/2070), ≥75 4.0% (47/1182); P 0.001). Age was an independent risk factor for 3-year mortality. Patients 65-74 did not have adjusted mortality higher than those65, yet age ≥75 was associated with increased overall mortality (Hazard ratio (HR) 1.47 (95% CI 1.30-1.68)) and cancer-specific mortality (HR 1.30 (95% CI 1.13-1.49)).Although advancing age was associated with higher rates of 90-day mortality following liver resection, 3-year mortality for patients 65-74 years was comparable to younger patients. These results will aid clinicians and patients in pre-operative decision-making.

BackgroundRecent evidence indicates that a preoperative warm-up is a potentially useful tool in facilitating performance. But what factors drive such improvements and how should a warm-up be implemented?MethodsIn order to address these issues, we adopted a two-pronged approach: (1) we conducted a systematic review of the literature to identify existing studies utilising preoperative simulation techniques; (2) we performed task analysis to identify the constituent parts of effective warm-ups. We identified five randomised control trials, four randomised cross-over trials and four case series. The majority of these studies reviewed surgical performance following preoperative simulation relative to performance without simulation.ResultsFour studies reported outcome measures in real patients and the remainder reported simulated outcome measures. All but one of the studies found that preoperative simulation improves operative outcomes—but this improvement was not found across all measured parameters. While the reviewed studies had a number of methodological issues, the global data indicate that preoperative simulation has substantial potential to improve surgical performance. Analysis of the task characteristics of successful interventions indicated that the majority of these studies employed warm-ups that focused on the visual motor elements of surgery. However, there was no theoretical or empirical basis to inform the design of the intervention in any of these studies.ConclusionsThere is an urgent need for a more rigorous approach to the development of “warm-up” routines if the potential value of preoperative simulation is to be understood and realised. We propose that such interventions need to be grounded in theory and empirical evidence on human motor performance.

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.

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

AIM: To assess the clinical impact of 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) positronemission tomographyecomputed tomography (PET-CT) in patients with potentially resectable metastatic colorectal cancer. MATERIALS AND METHODS: One hundred and two patients with potentially resectable metastatic colorectal cancer underwent FDG PET-CT in addition to conventional imaging over an 18-month period. The findings were compared to conventional imaging, with histological or clinico-radiological validation. The impact on subsequent management was evaluated using information from clinico-radiological databases. RESULTS: Of 102 patients (mean age 67 years, range 27e85 years), 94 had liver, five had isolated lung, and three had limited peritoneal metastases. In 31 patients (30%) PET-CT had a major impact on subsequent management, by correctly clarifying indeterminate lesions on conventional imaging as inoperable metastatic disease in 16 patients, detecting previously unsuspected metastatic disease in nine patients, identifying occult second primary tumours in three patients, and correctly down-staging three patients. PET-CT had a minor impact in 12 patients (12%), no impact in 49 cases (48%), and a potentially negative impact in 10 cases (10%). Following PET-CT, 36 (35%) patients were no longer considered for surgery. Of those remaining operative 45 of 66 (68%) underwent potentially curative metastatic surgery. In this cohort PET-CT saved 16 futile laparotomies. CONCLUSION: FDG PET-CT has a valuable role in selected patients with metastatic colorectal cancer by improving staging accuracy and characterizing indeterminate lesions and helps triage patients to the appropriate treatment.

There have been evolutionary changes in the management of pathological conditions of the hepatobiliary system over recent years, particularly with an increasing emphasis on modern hepatobiliary surgical techniques. Concurrent advances have occurred in imaging technology and availability, leading to a greater use of ultrasound, multidetector computed tomography (CT), and magnetic resonance imaging (MRI) in the primary evaluation of hepatobiliary disease. Radionuclide imaging using technetium(99m) (Tc(99m)) hepatobiliary iminodiacetic acid (HIDA) derivatives is an established technique that complements morphological imaging, providing valuable functional information in both pre- and postoperative evaluation of patients with suspected or known hepatobiliary disease. This review discusses the current clinical indications for Tc(99m) HIDA scintigraphy using clinical cases to demonstrate how this technique continues to play a valuable diagnostic role in the assessment of the functional integrity of the hepatobiliary system.

Background The impact of computed tomography (CT)-based follow-up for the detection of resectable disease recurrence following surgery for colorectal liver metastases (CRLM) was evaluated. Methods Some 705 patients undergoing resection of CRLM between January 1993 and March 2007 were included. Surveillance comprised 3-monthly CT (thorax, abdomen and pelvis) in the first 2 years after surgery, 6 monthly for 3 years and annually from years 6 to 10. Survival differences following recurrence between patients managed surgically and palliatively were determined, and the cost was calculated. Results Five-year disease-free and overall survival rates were 28·3 and 32·3 per cent respectively. Of 402 patients who developed recurrence within 2 years, 88 were treated with liver resection alone and 36 with lung and/or liver resection. Their 5-year overall survival rates were 31 and 30 per cent respectively, compared with 3·9 per cent in 278 patients managed palliatively (P < 0·001). For each 3-month interval during the first year of follow-up, patients with recurrence treated surgically had better overall survival than those treated palliatively. The cost of surveillance that identified 124 patients amenable to further resection was £12 338 per operated recurrence. Assuming that patients with recurrence gained 5 years' survival, the mean survival gain was 4·28 years per resection and the cost per life-year gained was £2883. Conclusion Intensive 3-monthly CT surveillance after liver resection for CRLM detects recurrence that is amenable to further resection in a considerable number of patients. These patients have significantly better survival with a reasonable cost per life-year gained.

Introduction A solution under development at our institute, based on phosphate-buffered sucrose, has shown good preservation for kidneys and livers. This work used a refined version of this solution (PBSH—phosphate-buffered sucrose for the heart) in heart preservation, comparing it to solutions already widely used (University of Wisconsin, St. Thomas's, and Celsior solutions). Methods Following an initial washout phase and control working mode on a Langendorff system, hearts were flushed with preservation solution and after 6 hours at 4°C were then reperfused for 15 minutes followed by working heart mode for a further 30 minutes. Hemodynamic parameters were measured and compared with their preischemic values and expressed as percentage recovery. Enzyme measurement came from the collection of the initial 1.5 mL of the coronary effluent after the storage period. This was to test for creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). Hearts were then placed immediately into liquid nitrogen for adenosine triphosphate (ATP), lactate, and creatine phosphate (CP) testing. Spectrophotometric analysis was used to assess both the release of CPK and LDH into the coronary effluent, and the level of ATP, lactate, and CP in the frozen heart tissue. Results These results show that hearts that are preserved in PBSH are hemodynamically as well preserved as the hearts preserved in other solutions tested and their enzyme and lactate content is lower while having higher levels of energy compounds in these hearts. Conclusion Overall these results show that PBSH is at least as effective in cardiac preservation in the rat model of 6 hours of cold ischemia as these other widely used solutions tested.

Background and Purpose Cold flush preservation prolongs tissue viability during ischemia. However, there is little understanding of the effects of various preservation fluids on events during this period. A study of cold ischemia in rat livers was undertaken to compare biochemical and histological changes over time, using three preservation solutions: University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), and Leeds solution (LS) under development at our institution. Leeds solution is a phosphate-based sucrose solution that like UW contains the impermeant lactobionate and the metabolite allopurinol (1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) which acts as a competitive inhibitor of xanthine oxidase, stopping the breakdown of hypoxanthine to xanthine by oxidizing it to alloxanthine, inhibiting both the conversion of hypoxanthine to xanthine and the conversion of xanthine to uric acid. Materials and Methods At various time points, samples were analyzed for adenosine triphospate (ATP) and metabolites by high-performance liquid chromatography as well as for histological changes. Results In all livers, ATP, ADP, and AMP degraded over 4 hours. In UW and LS groups, degradation beyond hypoxanthine was halted, and it continued in the HTK group. This blockade led to a significant reduction in the accumulation of xanthine and uric acid. Histological analysis showed protected architecture and maintenance of reticulin scaffolds in the UW and LS groups, whereas tissue breakdown was seen from earlier time points in the HTK group. Additionally, throughout ischemia, signs of pathological injury were more pronounced with UW- than with LS-preserved tissue. Conclusions These results implied that cold ischemia in the liver is characterized by dynamic biochemical changes coincident with pathological injury which are initiated from the time of organ perfusion and influenced by the choice of the perfusion fluid. Allopurinol in UW and LS appears to be critical. We hypothesized that it may also affect the degree of subsequent reperfusion injury. The data supported the assertion that LS offerred improved preservation over UW, adding to the impetus to shorten ischemic times in clinical transplantation.

Background Several articles have compared histidine-tryptophan-ketoglutarate solution (HTK) with other preservation solutions in both liver and kidney transplantation, and the results suggest that HTK is as good or better than the criterion standard University of Wisconsin solution (UW) for short periods of cold ischemia, such as in live donation, but that it is not so efficient for longer periods of cold ischemia, causing a higher incidence of delayed graft function. Objective To evaluate energy levels, metabolites, and histologic findings to determine why HTK is inefficient for longer periods of cold ischemia. Methods Rat livers were perfused with either HTK or UW, and at various times, tissue samples were obtained for analysis of adenine triphosphate and metabolites using high-performance liquid chromatography or for histologic analysis. Results The high energy charge observed with HTK-perfused livers plateaued after 5 minutes, and by 60 minutes began to decrease, following the same trend as other samples. The plateau is due to excess available glucose; however, after 1 hour, it is beginning to be consumed. Low levels of uridine, required for glycogen synthesis, are found in HTK-perfused livers, which suggests that at reperfusion, there is none available, whereas the higher concentrations found in UW-perfused livers may be advantageous after reperfusion. This will be especially detrimental to use of HTK because glycogen is used up rapidly because of the presence of α-ketoglutarate in the solution, enabling continuation of the tricarboxylic acid cycle. Conclusions Overall, HTK seems to do well for the first 2 hours, after which any advantage observed initially starts to disappear. A liver perfused in HTK and transplanted after more than 1 hour reacts like an organ from an individual who has been starved, because of the low energy charge and absence of a glycogen store or ability to synthesis glycogen because of lack of uridine. Livers perfused with UW demonstrate higher levels of uridine and do not lose their glycogen content to the same extent as HTK-perfused livers. These findings explain in part why HTK sometimes causes delayed graft function after longer periods of cold ischemia.

Grafts from donation after cardiac death (DCD) donors are used to increase the number of organs available for liver transplantation. There is concern that warm ischemia may impair graft function. We compared our DCD recipients with a case-matched group of donation after brain death (DBD) recipients. Between January 2002 and April 2008, 39 DCD grafts were transplanted. These were matched with 39 DBD recipients on the basis of identified variables that had a significant impact on mortality. These were used to individually match DCD and DBD patients with similar predictive mortality. We compared patient/graft survival, primary non-function (PNF), and rates of complications. Of all liver transplants, 6.1% were DCD grafts. PNF occurred twice in the DCD group. The incidence of nonanastomotic biliary strictures (NABS; 20.5% versus 0%, P = 0.005) and hepatic artery stenosis (HAS; 12.8% versus 0%, P = 0.027) in the DCD group was higher. One-year (79.5% versus 97.4%, P = 0.029) and 3-year (63.6% versus 97.4%, P = 0.001) graft survival was lower in the DCD group. Three-year patient survival was also lower (68.2% versus 100%, P < 0.0001). Our study is the first to use case-matched patients and compare groups with similar predictive mortality. There was a higher incidence of NABS and HAS in the DCD group. NABS were likely a result of warm ischemia. HAS may have been due to ischemia or arterial injury during retrieval. The DCD group had significantly poorer outcomes, but DCD grafts remain a valuable resource. With careful donor/recipient selection, minimization of ischemia, and good postoperative care, acceptable results can be achieved.

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

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

Background Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long-term outcome after liver resection for colorectal liver metastasis (CRLM). Methods All patients undergoing resection for CRLM in 1993–2006, for whom data on IPM were recorded, were included in the study. A total of 563 patients was available for analysis. Results IPM was performed in 289 (51·3 per cent) of the patients. The duration of IPM ranged from 2 to 104 (median 22) min. There were no differences in clinicopathological features or postoperative morbidity between patients who had an IPM and those who did not. The median survival of patients undergoing IPM was 55·7 months compared with 48·9 months in those not having an IPM (P = 0·406). There was no difference in median disease-free survival between the two groups (22·1 versus 19·9 months respectively; P = 0·199). Conclusion IPM is not associated with an adverse long-term prognosis in patients undergoing liver resection for CRLM.

To identify whether positive resection margin tumours had a more aggressive phenotype, using tumour micro-vessel density and invasive margin.Archival tissue was retrieved from 109 patients who had undergone resection for colorectal liver metastases. The nature of the invasive margin was determined by HE histochemistry. MVD was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome were retrieved and collated with invasive margin and MVD data in a statistical database.41/68 patients with a positive resection margin (R1) had recurrences following liver resection, while only 16/41 patients with a clear margin (R0) developed recurrences. More of the margin clear patients also developed capsulated liver metastases (56%), compared to positive resection margin patients (22%) (Chi squared test p0.001). The stromal margin MVD in the R0 patients was 250 (11-609), compared to the R1 value of 122 (27-428) (Mann-Whitney U test p=0.01).Positive resection margin, amongst other factors, is a predictor of poor prognosis. This appears to be in part explained by the expression of adverse tumour characteristics.

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

Background Few studies are available on the effect of steatosis on perioperative outcome following hepatic resection for colorectal liver metastasis (CRLM). Methods Patients undergoing resection for CRLM from January 2000 to September 2005 were identified from a hepatobiliary database. Data analysed included laboratory measurements, extent of hepatic resection, blood transfusion requirements and steatosis. Results There were 386 patients with a median age of 66 (range 32–87) years, of whom 201 had at least one co-morbid condition and 194 had an American Society of Anesthesiologists grade of I. Anatomical resection was performed in 279 patients and non-anatomical resection in 107; 165 had additional procedures. Steatosis in 194 patients was classified as mild in 122, moderate in 60 and severe in 12. The overall morbidity rate was 36 per cent (139 patients) and the mortality rate was 1·8 per cent (seven patients). Admission to the intensive care unit, morbidity, infective complications and biochemical profile changes were associated with greater severity of steatosis. Independent predictors of morbidity were steatosis, extent of hepatic resection and blood transfusion. Conclusion Steatosis is associated with increased morbidity following hepatic resection. Other predictors of outcome were extent of hepatic resection and blood transfusion.

Background: The outcome of surgical intervention for hepatic metastases from gastrointestinal stromal tumours (GIST) is still uncertain. This study evaluated the outcome of patients following aggressive surgical resection and Imatinib mesylate therapy (IM). Patients and methods: This was a retrospective analysis of patients managed with hepatic metastases from GIST over a 13-year period (January 1993 to December 2005). Results: Twelve patients were identified with a median age at diagnosis of 62 (32–78) years. The primary sites of GIST were stomach (n= 5), jejunum (n= 4), sigmoid (n= 1), peritoneum (n= 1) and pancreas (n= 1). Eleven patients underwent surgical resection with curative intent and one patient had cytoreductive surgery. Following surgery with curative intent (n= 11), the overall 2- and 5-year survival rates were both 91%, whereas the 2- and 5-year disease-free rates following primary hepatic resection were 30% and 10%, respectively. The median disease-free period was 17 (3–72) months. Eight patients had recurrent disease and were managed with further surgery (n= 3), radiofrequency ablation (RFA) (n= 2) and IM (n= 8). Overall, there are four patients who are currently disease-free: two patients following initial hepatic resection and two patients following further treatment for recurrent disease. There was no significant association in clinicopathological characteristics between patients with recurrent disease within 2 years and patients who were disease-free for 2 years or more. Overall morbidity was 50% (n= 6), with one postoperative death. The follow-up period was 43 (3–72) months. Conclusion: Surgical resection for hepatic GIST metastases may improve survival in selected patients. Recurrent disease can be managed with surgery, RFA and IM.

There is increasing evidence that systemic inflammatory response has a positive correlation with a poorer outcome in patients undergoing resection for solid tumours. The aim of this study was to analyse the impact of an elevated C-reactive protein (CRP), an outcome following curative resection for colorectal liver metastases. One hundred and seventy patients who underwent curative resection for colorectal liver metastases were included in the study. Laboratory measurements of haemoglobin, white cell, platelets, albumin and CRP were taken on the day before surgery. Elevated CRP (10 mg l(-1)) was present in 54 (31.8%) patients. The median survival of patients with an elevated CRP was 19 months (95% CI 7.5-31.2 months) compared to 42.8 months (95% CI 33.2-52.5 months) for those with a normal CRP, P=0.004. Similarly, when assessing disease-free survival, patients with an elevated CRP had poorer disease-free survival (median of 11.8 months (95% CI 6.4-17.3) compared to median of 15.1 months (95% CI 11.1-19.1)), P=0.043. The result of the study showed that an elevated preoperative CRP is a predictor of poor outcome in patients undergoing curative resection for colorectal liver metastases.

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

Aim We undertook this study to evaluate the influence of resection margin distance from metastases on survival and post-operative disease recurrence after hepatectomy for colorectal liver metastasis. Methods Between January 1993 and December 2001, 293 consecutive patients underwent primary liver resection for colorectal metastasis. Clinical, pathological and outcome data were analysed using a prospectively collected database. Cases were stratified into those with involved and non-involved resection margins. Different non-involved margin widths were analysed against survival, recurrence rate and pattern (hepatic, extra hepatic) of recurrence. Results The 1, 3, 5 and 10 years actuarial survival rates were 82, 58, 44 and 36%, respectively. The median survival was 46 months. The histological liver resection margin involvement was a significant predictor of survival and disease free survival after surgery. One, two, five and 10 millimetres disease free resection margin widths were found not to be significant in influencing patients' survival or recurrence rate. Conclusion A positive hepatic resection margin was associated with a higher incidence of post-operative recurrence and lower survival rate. The width of the resection margin did not influence the post-operative recurrence rate or pattern of recurrence. The ‘1 cm rule’ should be abandoned.

In kidney transplantation, cold storage is the dominant modality used to prolong organ viability ex vivo, but is inevitably followed by a period of warm ischemia. Preservation fluids limit tissue damage during the ischemic period, but there is little information on the influence of preservation fluids on the physiologic consequences of warm ischemia alone, or on the comparative ability of such preservation fluids to limit warm ischemic injury. In this study, warm ischemia was induced in rat kidneys by crossclamping the left renal pedicle for 45 min with contralateral nephrectomy. The ischemic kidneys were flushed with Euro-Collins (EC), hyper osmolar citrate (HOC), University of Wisconsin (UW), or phosphate buffered sucrose (PBS)140 solution. Over a period of 2 h after reperfusion, urine and blood samples were collected and physiological parameters related to the function of the postischemic kidneys were assessed. The data show that postischemic renal function can be influenced by the choice of preservation fluid. Essentially, the continued use of EC as a renal preservation solution finds little support in these data, and, while HOC and UW solutions were better able to limit the decline in renal function after warm ischemia than EC, the solution most able to limit functional impairment after warm ischemia was PBS140. This analysis compares the efficacies of the commonly used preservation solutions and could form the basis for future solid-organ transplant studies that may ultimately allow us to propose best-practice guidelines and an optimum platform for improved preservation solutions.

Background In some patients undergoing right hepatic trisectionectomy for metastases, extension of the resection beyond the falciform ligament is necessary to achieve tumour clearance. The aim of the present study was to assess the early and long-term outcomes and hepatic function in patients who underwent extensive liver resection beyond right trisectionectomy. Methods Thirty-eight patients who had extension of a right trisectionectomy, either in contiguity (IC) or in a non-anatomical (NA) fashion, for liver metastases were included in the study. In-hospital mortality, hepatic function and other morbidity were recorded. Survival outcomes were analysed for the subgroup of patients with colorectal liver metastases. The clinical risk score described by the Memorial Sloan–Kettering Cancer Center was applied to all patients with colorectal liver metastases. Results Sixteen patients had IC resection, 15 NA resection, and seven had both IC and NA procedures. There was one in-hospital death. Hepatic dysfunction was seen in 25 patients and two developed liver failure. Disease-free actuarial 3-year survival was 42 per cent for patients with colorectal liver metastases. Survival was significantly better in patients with a clinical risk score of 3 or less. Conclusion Extension of right trisectionectomy for liver metastases was associated with a low risk of death and hepatic failure.

Background In recent years, several reports from North America have highlighted the success of conservative treatment in patients with blunt liver trauma. The aim of this study was to identify trends in the management of blunt liver trauma in a UK tertiary referral centre dealing with both adults and children over a 10-year period. Methods A retrospective case note review was performed on 71 consecutive patients (58 male patients) of median age 25 years admitted to the hepatobiliary unit over the 10-year period from 1992 to 2001 with blunt liver trauma. Data relating to referring source, severity of liver injury, initial and subsequent management and outcome were collected using a standard pro forma. Results Sixty-two of the 71 patients were referred from other surgical units. Of these, 14 had undergone laparotomy at the referring hospital, with ten having perihepatic packing; the other 48 were managed conservatively. Of the 62 patients transferred to the authors' unit, 12 required surgical intervention for the liver injury. The mean number of patients with blunt liver trauma increased between the first second 5-year periods, from 3·2 to 11·0 patients per year. There was a significant reduction in the proportion of patients requiring surgery for the liver injury in both the authors' unit (from seven of 16 patients in 1992–1996 to seven of 55 in 1997–2001; P = 0·017, χ2 test) and referring hospitals (from six of 12 to eight of 50; P = 0·014, χ2 test). The reduction in the mortality rate, from two (12·5 per cent) of 16 in the first period to four (7·3 per cent) of 55 in the second, was not significant (P = 0·880, χ2 test). Conclusion This study demonstrated a marked increase in the number of patients with blunt liver trauma referred to a regional hepatobiliary centre in recent years. It has confirmed that the majority of such patients can be treated successfully without surgery.

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.

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 χ2 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.

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.

This study was designed to determine the impact of positive margin and neoadjuvant chemotherapy (NAC) on recurrence and survival after resection of colorectal liver metastasis (CRLM). Prospective analysis of 1,255 patients undergoing resection of CLRM was undertaken. The impact of NAC, site of recurrence, and survival between R0 and R1 groups was analysed. The R0 and R1 resection rates were 68.9 % (n = 865) and 31.1 % (390). The median OS for R0 group was 2.7 years (95 % CI 2.56–2.85) and R1 group 2.28 years (CI 2.06–2.52; P

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

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n=25; score 2, n=29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan–Meier survival analysis and log rank test, both P=0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.

The urological complications of renal transplantation are well documented. In 1990, our experience of 507 consecutive renal transplants using the Leadbetter-Politano technique, which was unsplinted in the vast majority of patients, had a ureteric complication rate of 7.7%. Here, we report the long-term incidence and management of our ureteric complications in 1186 consecutive renal transplants done over the following 11 years using an extravesical onlay stented ureteroneocystostomy. We report a considerable reduction in the urological complications of renal transplantation to 3.8%. Furthermore, we were able to use percutaneous radiological techniques to salvage the majority (84.7%) of ureteric complications. Recourse to surgery was required rarely but enabled salvage of all treatment failures.

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.

Background Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. Methods A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. Results A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). Conclusion Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.