Showing papers by "Brian R. Davidson published in 2009"

Assessment of risk of bias in randomized clinical trials in surgery

Abstract: Background: Meta-analysis of randomized clinical trials (RCTs) with low risk of bias is considered the highest level of evidence available for evaluating an intervention. Bias in RCTs may overestimate or underestimate the true effectiveness of an intervention. Methods: The causes of bias in surgical trials as described by The Cochrane Collaboration, and the methods that can be used to avoid them, are reviewed. Results: Blinding is difficult in many surgical trials but careful trial design can reduce the bias risk due to lack of blinding. It is possible to conduct surgical trials with low risk of bias by using appropriate trial design. Conclusion: The risk of providing a treatment based on a biased effect estimate must be balanced against the difficulty of conducting trials with very low risk of bias. Better understanding of the risk of bias may result in improved trials with a closer estimate of the true effectiveness of an intervention. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

Abstract: Portal vein embolisation (PVE) is used to increase the remnant liver volume before major liver resection for colorectal metastases. The resection rate after PVE is 60–70%, mainly limited by disease progression. The effect of PVE on tumour growth rate has not been investigated. The objective of this study was to compare the growth characteristics of resected colorectal liver metastases in patients undergoing pre-operative PVE with those of matched controls who had not undergone PVE. There were 22 patients who had undergone preoperative PVE and 20 matched controls. Tumour growth rate was calculated by the change in tumour volume (CT/MRI volumetric assessment) from diagnosis to resection. Resected histological specimens were examined by two histopathologists independently for cell differentiation, percentage tumour cell necrosis and mitotic rate. Immunochemical staining with Ki67 was carried out using the MIB-1 monoclonal antibody and quantified using a Glasgow cell-counting graticule. The groups were comparable in demographics, stage of primary disease, volume of liver metastases at presentation and chemotherapy received. The tumour growth rate calculated from imaging was more rapid in the PVE group compared with that in controls (control: 0.05±0.25 ml day−1, PVE: 0.36±0.68 ml day−1, P=0.06). Histology showed no difference in the degree of differentiation, extent of necrosis or apoptosis between the two groups. However, mitotic rate was higher post PVE, as was the proliferation index Ki67 (P=0.04). This study has confirmed that tumour growth rate increased following PVE and that this is related to increased tumour cell division.

Techniques for liver parenchymal transection in liver resection.

Abstract: Background Blood loss during elective liver resection is one of the main factors affecting the surgical outcome. Different parenchymal transection techniques have been suggested to decrease blood loss. Objectives To assess the benefits and risks of the different techniques of parenchymal transection during liver resections. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (March 2008). Selection criteria We considered for inclusion all randomised clinical trials comparing different methods of parenchymal dissection irrespective of the method of vascular occlusion or any other measures used for lowering blood loss. Data collection and analysis Two authors identified the trials and extracted the data on the population characteristics, bias risk, mortality, morbidity, blood loss, transection speed, and hospital stay independently of each other. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals based on 'interntion-to-treat analysis' or 'available case analysis' using RevMan 5. Main results We included seven trials randomising 556 patients. The comparisons include CUSA (cavitron ultrasound surgical aspirator) versus clamp-crush (two trials); radiofrequency dissecting sealer (RFDS) versus clamp-crush (two trials); sharp dissection versus clamp-crush technique (one trial); and hydrojet versus CUSA (one trial). One trial compared CUSA, RFDS, hydrojet, and clamp-crush technique. The infective complications and transection blood loss were greater in the RFDS than clamp-crush. There was no difference in the blood transfusion requirements, intensive therapy unit (ITU) stay, or hospital stay in this comparison. There was no significant differences in the mortality, morbidity, markers of liver parenchymal injury or liver dysfunction, ITU, or hospital stay in the other comparisons. The blood transfusion requirements were lower in the clamp-crush technique than CUSA and hydrojet. There was no difference in the transfusion requirements of clamp-crush technique and sharp dissection. Clamp-crush technique is quicker than CUSA, hydrojet, and RFDS. The transection speed of sharp dissection and clamp-crush technique was not compared. There was no clinically or statistically significant difference in the operating time between sharp dissection and clamp-crush techniques. Clamp-crush technique is two to six times cheaper than the other methods depending upon the number of surgeries performed each year. Authors' conclusions Clamp-crush technique is advocated as the method of choice in liver parenchymal transection because it avoids special equipment, whereas the newer methods do not seem to offer any benefit in decreasing the morbidity or transfusion requirement.

Methods of vascular occlusion for elective liver resections

Abstract: BackgroundVascular occlusion is used to reduce blood loss during liver resection surgery. Various methods of vascular occlusion have been suggested.ObjectivesTo compare the benefits and harms of different methods of vascular occlusion during elective liver resection.Search strategyWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2008.Selection criteriaWe included randomised clinical trials comparing different methods of vascular occlusion during elective liver resections (irrespective of language or publication status).Data collection and analysisTwo authors independently assessed trials for inclusion and independently extracted the data. We calculated the risk ratio or mean difference with 95% confidence intervals using fixed-effect and random-effects models based on intention-to-treat or available data analysis.Main resultsTen trials including 657 patients compared different methods of vascular occlusion. All trials were of high risk of bias. Only one or two trials were included under each comparison. There was no statistically significant differences in mortality, liver failure, or other morbidity between any of the comparisons.Hepatic vascular occlusion does not decrease the blood transfusion requirements. It decreases the cardiac output and increases the systemic vascular resistance. In the comparison between continuous portal triad clamping and intermittent portal triad clamping, four of the five liver failures occurred in patients with chronic liver diseases undergoing the liver resections using continuous portal triad clamping. In the comparison between selective inflow occlusion and portal triad clamping, all four patients with liver failure occurred in the selective inflow occlusion group. There was no difference in any of the other important outcomes in any of the comparisons.Authors' conclusionsIn elective liver resection, hepatic vascular occlusion cannot be recommended over portal triad clamping. Intermittent portal triad clamping seems to be better than continuous portal triad clamping at least in patients with chronic liver disease. There is no evidence to support selective inflow occlusion over portal triad clamping. The optimal method of intermittent portal triad clamping is not clear. There is no evidence for any difference between the ischaemic preconditioning followed by vascular occlusion and intermittent vascular occlusion for liver resection in patients with non-cirrhotic livers. Further randomised trials of low risk of bias are needed to determine the optimal technique of vascular occlusion.

Liver resection versus other treatments for neuroendocrine tumours in patients with resectable liver metastases

Abstract: Background Neuroendocrine tumours are tumours of cells, which possess secretory granules and originate from the neuroectoderm. While liver resection is generally advocated in patients with resectable liver metastases, recent studies have shown good survival in patients with disseminated neuroendocrine tumours who underwent thermal ablation using radiofrequency. Objectives To determine the benefits and harms of liver resection versus other treatments in patients with resectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours. Search strategy We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS until July 2008 for identifying the randomised trials. Selection criteria We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing liver resection (alone or in combination with radiofrequency ablation or cryoablation) versus other interventions (chemotherapy, hormonotherapy, or immunotherapy) and those comparing liver resection and thermal ablation (radiofrequency ablation or cryoablation) in patients with resectable liver metastases from neuroendocrine tumours for the review. Data collection and analysis Two authors independently identified trials for inclusion. Main results We were unable to identify any randomised clinical trial suitable for inclusion in this review. We were also unable to identify any quasi-randomised studies, cohort studies, or case-control studies that could inform meaningfully. Authors' conclusions There is no evidence from randomised clinical trials comparing liver resection versus other treatments in patients with resectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours. Liver resection appears to be the main stay curative treatment for neuroendocrine liver metastases based on non-randomised studies. Further randomised clinical trials comparing liver resection alone or in combination with chemoembolisation or radionuclide therapy are needed. Further randomised clinical trials comparing surgical resection and radiofrequency ablation in selected patients may also be appropriate.

Long-Term Survival and Disease Recurrence Following Portal Vein Embolisation Prior to Major Hepatectomy for Colorectal Metastases

Abstract: Background Portal vein embolisation (PVE) can be used to increase the remnant liver parenchyma volume before major hepatectomy but may stimulate tumour growth. The pattern of disease recurrence and long-term survival has not been adequately addressed.

Techniques for liver parenchymal transection: a meta-analysis of randomized controlled trials

Abstract: Background Different techniques of liver parenchymal transection have been described, including the finger fracture, sharp dissection, clamp–crush methods and, more recently, the Cavitron ultrasonic surgical aspirator (CUSA), the hydrojet and the radiofrequency dissection sealer (RFDS). This review assesses the benefits and risks associated with the various techniques. Methods Randomized clinical trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Odds ratio (ORs), mean difference (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals based on intention-to-treat analysis or available-case analysis. Results We identified seven trials including a total of 556 patients. Blood transfusion requirements were lower with the clamp–crush technique than with the CUSA or hydrojet. The clamp–crush technique was quicker than the CUSA, hydrojet or RFDS. Infective complications and transection blood loss were greater with the RFDS than with the clamp–crush method. There was no significant difference between techniques in mortality, morbidity, liver dysfunction or intensive therapy unit and hospital stay. Conclusions The clamp–crush technique is more rapid and is associated with lower rates of blood loss and otherwise similar outcomes when compared with other methods of parenchymal transection. It represents the reference standard against which new methods may be compared.

Fibrolamellar hepatocellular carcinoma: prolonged survival with multimodality therapy.

Abstract: Aim We report the clinical outcome for a series of ten patients with fibrolamellar hepatocellular treated with resection followed by close surveillance and aggressive management of relapse. Methods The case notes for all patients treated at this institution since 1982 were reviewed and details of initial stage and management were extracted along with investigations and treatment of relapse. Time to relapse, overall survival and post-relapse survival were analysed. Results Relapse occurred in all ten cases at a median of 2.2 (95% CI 0.9–2.7) years but, with a combination of re-resection, systemic chemotherapy and radiotherapy, the overall median survival was 9.3 (95% CI 3.0–18.5) years. One patient was disease free eight years after two resections for recurrent disease. Two of nine patients had a partial response to cisplatin and fluorouracil while three had stable disease. FDG-PET was positive for recurrence in three of four cases of relapse, and in one case detected recurrence in advance of CT. Conclusion The early detection of relapse combined with multimodality therapy results in prolonged survival. Further improvements in systemic therapy are required to improve the prognosis in this disease.

Serum C-reactive protein concentration and the prognosis of ductal adenocarcinoma of the head of pancreas

Abstract: Background The prognostic role of serum C-reactive protein in pancreatic cancer has received increasing attention; however the confounding effects of biliary obstruction have not been addressed in previous studies. We sought to determine the prognostic importance of serum CRP prior to biliary intervention in the prognosis of pancreatic adenocarcinoma. Methods A retrospective case note review of patients diagnosed with pancreatic cancer between 2001 and 2006. Clinical, radiological and biochemical criteria were correlated with overall survival. Patients were divided into: Group 1 who underwent potentially curative resection, and Group 2 with advanced unresectable disease managed non-surgically. Results In total, 199 patients were included (58 resected). The proportion of patients with biliary obstruction was equal in both groups. Serum CRP and serum bilirubin concentration at presentation were significantly higher among patients in Group 2 compared to Group 1 ( P values). On multivariate analysis, advancing age ( P = 0.012) and raised serum CRP concentration were independently associated with overall survival only in Group 2 patients ( P = 0.027, 95% CI 0.31–0.93). This association was independent of biliary tract obstruction. Conclusion Raised serum C-reactive protein concentration at the time of presentation of advanced pancreatic cancer carries a poor prognosis independent of biliary tract obstruction.

Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury.

Abstract: Background Liver transplantation involves a period of ischemia and reperfusion to the graft which leads to primary non-function and dysfunction of the liver in 5–10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood flow. We hypothesized that RIPC may directly modulate hepatic microcirculation and have investigated this using intravital microscopy. Methods A rat model of liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were studied ( n = 6, each group). Intravital microscopy was used to measure red blood cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils and cell death using propidium iodide. Results RIPC reduced the effects of IRI by significantly increasing red blood cell velocity, sinusoidal flow and sinusoidal perfusion along with decreased neutrophil adhesion and cell death. Conclusions Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function.

Ischaemic pre-conditioning for elective liver resections performed under vascular occlusion.

Abstract: Background Vascular occlusion is used to reduce blood loss during liver resection surgery. The enzyme markers of liver injury are elevated if vascular occlusion is employed during liver resection. It is not clear whether ischaemic preconditioning prior to vascular occlusion has a protective effect during elective liver resections. Objectives To assess the advantages (decreased ischaemia-reperfusion injury) and any potential disadvantages of ischaemic preconditioning prior to vascular occlusion during liver resections. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2008. Selection criteria We included randomised clinical trials comparing ischaemic preconditioning versus no ischaemic preconditioning prior to vascular occlusion (irrespective of the method of vascular occlusion) during elective liver resections (irrespective of language or publication status). Data collection and analysis Two authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We calculated the risk ratio, mean difference, or standardised mean difference with 95% confidence intervals based on intention-to-treat or available data analysis. Main results We included four trials with 271 patients undergoing open liver resections. The patients were randomised to ischaemic preconditioning (n = 135) and no ischaemic preconditioning (n = 136) prior to continuous vascular occlusion (portal triad clamping in three trials and hepatic vascular exclusion in one trial). All the trials excluded cirrhotic patients. We assessed all the four trials as having high risk of bias. There was no difference in mortality, liver failure, other peri-operative morbidity, hospital stay, intensive therapy unit stay, and operating time between the two groups. The proportion of patients requiring blood transfusion was lower in the ischaemic preconditioning group. There was also a trend towards a lower amount of red cell transfusion favouring ischaemic preconditioning group. There was no difference in the haemodynamic changes, blood loss, bilirubin, or prothrombin activity between the two groups. The enzyme markers of liver injury were lower in the ischaemic preconditioning group on the first post-operative day. Authors' conclusions Currently, there is no evidence to suggest a protective effect of ischaemic preconditioning in non-cirrhotic patients undergoing liver resection under continuous vascular occlusion. Ischaemic preconditioning reduces the blood transfusion requirements in patients undergoing liver resection.

Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection.

Abstract: BackgroundBlood loss during liver resection is one of the most important factors affecting the peri-operative outcomes of patients undergoing liver resection.ObjectivesTo determine the benefits and harms of pharmacological interventions to decrease blood loss and to decrease allogeneic blood transfusion requirements in patients undergoing liver resections.Search strategyWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until November 2008 for identifying the randomised trials.Selection criteriaWe included all randomised clinical trials comparing various pharmacological interventions aimed at decreasing blood loss and allogeneic blood transfusion requirements in liver resection. Trials were included irrespective of whether they included major or minor liver resections, normal or cirrhotic livers, vascular occlusion was used or not, and irrespective of the reason for liver resection.Data collection and analysisTwo authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference with 95% confidence intervals (CI) based on intention-to-treat analysis or available case-analysis. For dichotomous outcomes with only one trial included under the outcome, we performed the Fisher's exact test.Main resultsSix trials involving 849 patients satisfied the inclusion criteria. Pharmacological interventions included aprotinin, desmopressin, recombinant factor VIIa, antithrombin III, and tranexamic acid. One or two trials could be included under most comparisons. All trials had a high risk of bias. There was no significant difference in the peri-operative mortality, survival at maximal follow-up, liver failure, or other peri-operative morbidity. The risk ratio of requiring allogeneic blood transfusion was significantly lower in the aprotinin and tranexamic acid groups than the respective control groups. Other interventions did not show significant decreases of allogeneic transfusion requirements.Authors' conclusionsNone of the interventions seem to decrease peri-operative morbidity or offer any long-term survival benefit. Aprotinin and tranexamic acid show promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias. Further randomised clinical trials with low risk of bias and random errors assessing clinically important outcomes such as peri-operative mortality are necessary to assess any pharmacological interventions aimed at decreasing blood loss and blood transfusion requirements in liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.

Palliative cytoreductive surgery versus other palliative treatments in patients with unresectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours.

Abstract: Background Neuroendocrine tumours are tumours of cells which possess secretory granules and originate from the neuroectoderm. While liver resection is generally advocated in patients with resectable liver alone metastases, the management of patients with liver metastases, which cannot be completely resected, is controversial. Objectives To determine if cytoreductive surgery is better than other palliative treatments in patients with liver metastases from gastro-entero-pancreatic neuroendocrine tumours, which cannot be completely resected. Search strategy We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until July 2008 for identifying the randomised trials. Selection criteria Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing liver resection (alone or in combination with radiofrequency ablation or cryoablation) versus other palliative treatments (chemotherapy or hormone-therapy or immunotherapy) or no treatment in patients with liver metastases from neuroendocrine tumours, which cannot be completely resected, were considered for the review. Data collection and analysis Two authors independently identified trials for inclusion. Main results We were unable to identify any randomised clinical trial suitable for inclusion in this review. Authors' conclusions The literature provides no evidence from randomised clinical trials in order to assess the role of cytoreductive surgery in non-resectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours. High-quality randomised clinical trials may become feasible to perform if their conduct and study design is thoroughly considered in all their practical and methodological aspects. Pilot randomised clinical trials, which can guide the study design of definitive randomised clinical trials, are necessary.

Vascular occlusion for elective liver resections

Abstract: BACKGROUND Vascular occlusion is used to reduce blood loss during liver resection. There is considerable controversy regarding whether vascular occlusion should be used or not during elective liver resections. OBJECTIVES To assess the advantages (decreased blood loss and peri-operative morbidity) and disadvantages (ischaemia-reperfusion injury related complications like liver dysfunction) of vascular occlusion during elective liver resections. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2008. SELECTION CRITERIA We included randomised clinical trials comparing vascular occlusion versus no vascular occlusion during elective liver resections (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS Two authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat or available case analysis. MAIN RESULTS We identified a total of five trials (of high bias-risk) which compared vascular occlusion (n = 166) versus no vascular occlusion (n = 165). Three of the five trials comparing vascular occlusion and no vascular occlusion used intermittent vascular occlusion. There was no difference in mortality, liver failure, or other morbidities. The blood loss was significantly lower in vascular occlusion compared with no vascular occlusion. The liver enzymes were significantly elevated in the vascular occlusion group compared with no vascular occlusion. AUTHORS' CONCLUSIONS Intermittent vascular occlusion seems safe in liver resection. However, it does not seem to decrease morbidity. More randomised trials seem to be needed.

Cholecystectomy for suspected gallbladder dyskinesia

Abstract: BackgroundThe optimal treatment for patients with suspected biliary dyskinesia is controversial. Some studies found that cholecystectomy produced symptomatic improvement in patients with gallbladder dyskinesia ( diagnosed by low gallbladder ejection fraction) while others found no significant benefit. Some studies have shown that gallbladder ejection fraction can discriminate patients who would benefit from cholecystectomy. Other studies have not confirmed this.ObjectivesThe aim of this review was to compare the benefits and harms of cholecystectomy for patients with suspected gall bladder dyskinesia.Search strategyWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Control led Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until March 2008.Selection criteriaWe considered for inclusion all randomised clinical trials comparing cholecystectomy versus no cholecystectomy on patients with gallbladder dyskinesia.Data collection and analysisWe collected the data on the characteristics, methodological quality, mortality, number of patients in whom symptoms were improved or cured from the one identified trial. We planned to analyse the data using the fixed-effect and the random-effects models using RevMan Analysis. For each outcome we planned to calculate the risk ratio (RR) with 95% confidence intervals based on intention-to-treat analysis.Main resultsWe included one trial with 21 patients randomised: 11 to cholecystectomy and 10 to control (no cholecystectomy). This trial was considered to be of high risk of bias as patients were not blinded and the procedure-related morbidity was not reported. There was no mortality in either group. All patients in the cholecystectomy group and only one patient in the control group had improvement in symptoms (P = 0.0001) after a mean follow-up period of 33.6 months.Authors' conclusionsThe evidence for the benefits and harms of cholecystectomy in gallbladder dyskinesia from randomised clinical trials is based on a single small trial at risk of bias. Further randomised clinical trials with improved bias control are necessary to confirm or reject the promising results.

Robot assistant for laparoscopic cholecystectomy

Abstract: BackgroundThe role of a robotic assistant in laparoscopic cholecystectomy is controversial. While some trials have shown distinct advantages of robotic assistant over a human assistant, others have not, and it is unclear which robotic assistant is best.ObjectivesThe aims of this review are to compare the safety of robot assistant versus human assistant in laparoscopic cholecystectomy and to assess whether the robot can substitute for the human assistant.Search strategyWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation In de x Expanded until May 2008 for identifying the randomised trials using The Cochrane Hepato-Biliary Group search strategy.Selection criteriaOnly randomised clinical trials (irrespective of language, blinding, or publication status) comparing robot assistants versus human assistants in laparoscopic cholecystectomy were considered for the review. Randomised clinical trials comparing different types of robot assistants were also considered for the review.Data collection and analysisTwo authors independently identified the trials for exclusion and independently extracted the data. We calculated the risk ratio, mean difference, or standardised mean difference with 95% confidence intervals using the fixed-effect and the random-effects models based on available case-analysis using RevMan 5.Main resultsWe included five trials (all of high risk of bias) with 453 patients randomised: 159 to the robot-assistant group and 165 to the human assistant group (one trial report of 129 patients was a conference abstract, not reporting on the number of patients in each group). There was no statistically significant difference between the two groups for morbidity, conversion to open cholecystectomy, total operating time, or hospital stay when fixed-effect or random-effects model were used. The instrument set-up time was significantly lower in the human assistant group. In one trial, about one sixth of the laparoscopic cholecystectomies in which robot assistant was used, required temporary use of a human assistant. It appears that there was little or no requirement for human assistants in the other three published trials. In two of the three trials, which reported surgeons' preference, the surgeons preferred a robot assistant to a human assistant. There was no statistically significant difference in the accuracy when the random-effects model was used. There was no difference in the errors.Authors' conclusionsAlthough robot-assisted laparoscopic cholecystectomy appears safe, there seems to be no significant advantages over human-assisted laparoscopic cholecystectomy. We were unable to identify trials comparing one type of robot assistant versus another. Further randomised trials with low bias-risk and random errors are needed.

Cholecystectomy for gallbladder polyp

Abstract: Background The management of gallbladder polyps is controversial Cholecystectomy has been recommended for gallbladder polyps larger than 10 mm because of the association with gallbladder cancer Cholecystectomy has also been suggested for gallbladder polyps smaller than 10 mm in patients with biliary type of symptomsObjectivesThe aim of this review is to compare the benefits (relief of symptoms, decreased incidence of gallbladder cancer) and harms (surgical morbidity) of cholecystectomy in patients with gallbladder polyp(s)Search strategyWe searched The Cochrane Hepato- Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until July 2008 to identify the randomised trialsSelection criteriaOnly randomised clinical trials (irrespective of language, blinding, or publication status) comparing cholecystectomy and no cholecystectomy were considered for the reviewData collection and analysisWe planned to collect the data on the characteristics, methodological quality, mortality, number of patients in whom symptoms were improved or cured from the one identified trial We planned to analyse the data using the fixed-effect and the random-effects models using RevMan Analysis For each outcome we planned to calculate the risk ratio (RR) with 95% confidence intervals based on intention-to-treat analysisMain resultsWe were unable to identify any randomised clinical trials comparing cholecystectomy versus no cholecystectomy in patients with a gallbladder polypAuthors' conclusionsThere are no randomised trials comparing cholecystectomy versus no cholecystectomy in patients with gallbladder polyps Randomised clinical trials with low bias-risk are necessary to address the question of whether cholecystectomy is indicated in gallbladder polyps smaller than 10 mm

Pharmacological interventions versus no pharmacological intervention for ischaemia reperfusion injury in liver resection surgery performed under vascular control.

Abstract: BACKGROUND: Vascular occlusion to reduce blood loss is used during elective liver resection but results in significant ischaemia reperfusion injury. This, in turn, might lead to significant postoperative liver dysfunction and morbidity. Various pharmacological drugs have been used with an intention to ameliorate the ischaemia reperfusion injury in liver resections. OBJECTIVES: To assess the benefits and harms of different pharmacological agents versus no pharmacological interventions to decrease ischaemia reperfusion injury during liver resections where vascular occlusion was performed during the surgery. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until January 2009. SELECTION CRITERIA: We included randomised clinical trials, irrespective of language or publication status, comparing any pharmacological agent versus placebo or no pharmacological agent during elective liver resections with vascular occlusion. DATA COLLECTION AND ANALYSIS: Two authors independently identified trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis. MAIN RESULTS: We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046 (a thromboxane A2 synthetase inhibitor)). All trials had high risk of bias. There were no significant differences between the groups in mortality, liver failure, or perioperative morbidity. The trimetazidine group had a significantly shorter hospital stay than control (MD -3.00 days; 95% CI -3.57 to -2.43). There were no significant differences in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared with controls. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias. AUTHORS' CONCLUSIONS: Trimetazidine, methylprednisolone, and dextrose may protect against ischaemia reperfusion injury in elective liver resections performed under vascular occlusion, but this is shown in trials with small sample sizes and high risk of bias. The use of these drugs should be restricted to well-designed randomised clinical trials before implementing them in clinical practice.

Pharmacological interventions for ischaemia reperfusion injury in liver resection surgery performed under vascular control

Abstract: Background: Vascular occlusion used during elective liver resection to reduce blood loss results in significant ischaemia reperfusion (IR) injury. This in turn leads to significant postoperative liver dysfunction and morbidity. Various pharmacological drugs have been used in experimental settings to ameliorate the ischaemia reperfusion injury in liver resections. Objectives: To assess the relative benefits and harms of using one pharmacological intervention versus another pharmacological intervention to decrease ischaemia reperfusion injury during liver resections where vascular occlusion was performed during the surgery. Search strategy: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until January 2009. Selection criteria: We included randomised clinical trials, irrespective of language or publication status, comparing one pharmacological agent versus another pharmacological agent during elective liver resections with vascular occlusion. Data collection and analysis: Two authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixedeffect and the random-effects models using RevMan Analysis. We planned to calculate the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis. However, all outcomes were only reported on by single trials, and meta-analysis could not be performed. Therefore, we performed Fisher's exact test on dichotomous outcomes. Main results: We identified a total of five randomised trials evaluating nine different pharmacological interventions (amrinone, prostaglandin E1, pentoxifylline, dopexamine, dopamine, ulinastatin, gantaile, sevoflurane, and propofol). All trials had high risk of bias. There was no significant difference between the groups in mortality, liver failure, or perioperative morbidity. The ulinastatin group had significantly lower postoperative enzyme markers of liver injury compared with the gantaile group. None of the other comparisons showed any difference in any of the other outcomes. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias. Authors' conclusions: Ulinastatin may have a protective effect against ischaemia reperfusion injury relative to gantaile in elective liver resections performed under vascular occlusion. The absolute benefit of this drug agent remains unknown. None of the drugs can be recommended for routine clinical practice. Considering that none of the drugs have proven to be useful to decrease ischaemia reperfusion injury, such trials should include a group of patients who do not receive any active intervention whenever possible to determine the pharmacological drug's absolute effects on ischaemia reperfusion injury in liver resections. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Methods of vascular occlusion for elective liver resections (Withdrawn Paper. 2009, art. no. CD006409)

Abstract: BACKGROUND Vascular occlusion is used to reduce blood loss during liver resection surgery. Various methods of vascular occlusion have been suggested. OBJECTIVES To compare the benefits and harms of different methods of vascular occlusion during elective liver resection. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2008. SELECTION CRITERIA We included randomised clinical trials comparing different methods of vascular occlusion during elective liver resections (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS Two authors independently assessed trials for inclusion and independently extracted the data. We calculated the risk ratio or mean difference with 95% confidence intervals using fixed-effect and random-effects models based on intention-to-treat or available data analysis. MAIN RESULTS Ten trials including 657 patients compared different methods of vascular occlusion. All trials were of high risk of bias. Only one or two trials were included under each comparison. There was no statistically significant differences in mortality, liver failure, or other morbidity between any of the comparisons.Hepatic vascular occlusion does not decrease the blood transfusion requirements. It decreases the cardiac output and increases the systemic vascular resistance. In the comparison between continuous portal triad clamping and intermittent portal triad clamping, four of the five liver failures occurred in patients with chronic liver diseases undergoing the liver resections using continuous portal triad clamping. In the comparison between selective inflow occlusion and portal triad clamping, all four patients with liver failure occurred in the selective inflow occlusion group. There was no difference in any of the other important outcomes in any of the comparisons. AUTHORS' CONCLUSIONS In elective liver resection, hepatic vascular occlusion cannot be recommended over portal triad clamping. Intermittent portal triad clamping seems to be better than continuous portal triad clamping at least in patients with chronic liver disease. There is no evidence to support selective inflow occlusion over portal triad clamping. The optimal method of intermittent portal triad clamping is not clear. There is no evidence for any difference between the ischaemic preconditioning followed by vascular occlusion and intermittent vascular occlusion for liver resection in patients with non-cirrhotic livers. Further randomised trials of low risk of bias are needed to determine the optimal technique of vascular occlusion.

WITHDRAWN: Methods of vascular occlusion for elective liver resections.

Abstract: BACKGROUND Vascular occlusion is used to reduce blood loss during liver resection surgery There is considerable controversy regarding whether vascular occlusion should be used or not during elective liver resections The method of vascular occlusion employed is also controversial There is also considerable debate on the role of ischaemic preconditioning before vascular occlusion OBJECTIVES To assess the advantages (decreased blood loss and peri-operative morbidity) and disadvantages (liver dysfunction from ischaemia) of vascular occlusion during liver resections To compare the advantages (in decreasing blood loss or decreasing ischaemia-reperfusion injury) and disadvantages of different types of vascular occlusion versus total, continuous portal triad clamping SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until March 2007 SELECTION CRITERIA We included randomised clinical trials comparing vascular occlusion versus no vascular occlusion during elective liver resections (irrespective of language or publication status) We also included randomised clinical trials comparing the different methods of vascular occlusion and those investigating the role of ischaemic preconditioning in liver resection DATA COLLECTION AND ANALYSIS We collected the data on the characteristics of the trial, methodological quality of the trials, mortality, morbidity, blood loss, blood transfusion requirements, liver function tests, markers of neutrophil activation, operating time, and hospital stay We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis For each binary outcome we calculated the odds ratio (OR) with 95% confidence intervals (CI) based on intention-to-treat analysis For continuous outcomes, we calculated the weighted mean difference (WMD) with 95% confidence intervals MAIN RESULTS We identified a total of 16 randomised trials Five trials including 331 patients compared vascular occlusion (n = 166) versus no vascular occlusion (n = 165) Six trials including 521 patients compared different methods of vascular occlusion Three trials including 210 patients compared ischaemic preconditioning before continuous portal triad clamping (n = 105) versus no ischaemic preconditioning (n = 105) Two trials including 127 patients compared ischaemic preconditioning before continuous portal triad clamping (n = 63) versus intermittent portal triad clamping (n = 64)The blood loss was significantly lower in vascular occlusion compared with no vascular occlusion The liver enzymes were significantly elevated in the vascular occlusion group compared with no vascular occlusion There was no difference in the mortality, liver failure, or other morbidities Four of the five trials comparing vascular occlusion and no vascular occlusion used intermittent vascular occlusion Trials comparing complete inflow and outflow occlusion to the liver, ie, hepatic vascular exclusion and portal triad clamping demonstrate significant detrimental haemodynamic changes in hepatic vascular exclusion compared to portal triad clamping There was no significant difference in the number of units transfused and the number of patients needing transfusion There was no difference in mortality, liver failure, or morbidity between total and selective methods of portal triad clamping All four cases of mortality and liver failure in the comparison between the intermittent and continuous portal triad clamping occurred in the continuous portal triad clamping (statistically not significant) Intermittent portal triad clamping does not increase the total blood loss or operating time compared to continuous portal triad clampingThere was no statistically significant difference in the mortality, liver failure, morbidity, blood loss, or haemodynamic changes between ischaemic preconditioning versus no ischaemic preconditioning before continuous portal triad clamping Liver enzymes used as markers of liver injury were significantly lower in the early post-operative period in the ischaemic preconditioning group The intensive therapy unit stay and hospital stay were statistically significantly lower in the ischaemic preconditioning group than in the no ischaemic preconditioning groupThere was no statistically significant difference in the mortality, liver failure, morbidity, intensive therapy unit stay, or hospital stay between ischaemic preconditioning before continuous portal triad clamping and intermittent portal triad clamping The blood loss and transfusion requirements were lower in the ischaemic preconditioning group Aspartate aminotransferase level was lower in the intermittent portal triad clamping group than the ischaemic preconditioning group on the third post-operative day There was no difference in the peak aspartate aminotransferase levels or in the aspartate aminotransferase levels on first or sixth post-operative days of aspartate aminotransferase AUTHORS' CONCLUSIONS Intermittent vascular occlusion seems safe in liver resection However, it does not seem to decrease morbidity Among the different methods of vascular occlusion, intermittent portal triad clamping has most evidence to support the clinical application Hepatic vascular exclusion cannot be recommended routinely Ischaemic preconditioning before continuous portal triad clamping may be of clinical benefit in reducing intensive therapy unit and hospital stay

A stepwise approach to the management of metastatic midgut carcinoid tumor

Abstract: The authors present a case of a 48-year-old man with a history of diarrhea, flushing and upper abdominal pain who was subsequently diagnosed with metastatic carcinoid tumor. The authors discuss the importance of a stepwise approach in a multi-disciplinary team setting to provide effective patient care. Background. A 48-year-old man presented with diarrhea, flushing, abdominal pain and weight loss of 10 kg over a 6-month period. He subsequently developed dyspnea on exertion. Investigations. Physical examination, laboratory tests, CT of the abdomen, liver biopsy, echocardiography, immunohistochemistry staining of the biopsy specimen for neuroendocrine markers including chromogranin A, synaptophysin and protein gene product 9.5, and 111In-pentetreotide scintigraphy (Octreoscan™). Diagnosis. Carcinoid tumor of midgut origin with large segment 3 liver metastasis. Carcinoid syndrome and carcinoid heart disease. Management. Symptomatic relief with somatostatin analog therapy and subsequent resection of the segment 3 liver metastasis. Tricuspid and pulmonary valve replacement.

Measurement of K, Fe, Cu and Zn levels in secondary colorectal liver cancer and surrounding normal liver tissue, and their potential as a tissue classifier

Abstract: An x-ray fluorescence (XRF) system utilising a synchrotron radiation source was used to quantify the levels of Fe, Cu, Zn and K in colorectal liver metastases and surrounding normal liver tissue as a possible mechanism for detecting cancer in a tissue biopsy. Sixty samples were measured and a lower level of all four elements was found in the cancer samples compared with that of the normal liver. The difference in levels of Zn, Fe, Cu and K between cancer and normal tissue was significant with p values of <0.01 for Zn, Fe and K, and 0.033 for Cu. The precision was estimated by repeated measurements yielding a precision of 96,91, 95 and 86% for Zn, Cu, Fe and K, respectively. The homogeneity of the distribution of elemental concentrations was assessed by measuring eight normal liver and eight cancer samples from the same patient. The variation of Zn, Cu, Fe and K levels between normal liver samples was 10.4, 15.4, 15.85 and 29.1%, respectively, and in the colorectal metastases was 10.18, 15.92, 8.44 and 22.35%, respectively. Receiver operator characteristic (ROC) analysis was performed for all elements and showed that Zn could be a reliable indicator of tissue classification with an ROC area under the curve of 0.998 and a resulting sensitivity and specificity of 100 and 96.67%, respectively. Fe had an ROC area under the curve of 0.856 and sensitivity and specificity of 83.3 and 76.67%, respectively. Cu and K did not perform as well with areas under the curve of 0.75 and 0.706, respectively. Copyright (C) 2008 John Wiley & Sons, Ltd.

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury.

Abstract: Background Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells. Methods The effect of bucillamine was studied in a rat model of liver ischaemia–reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM). Results The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P P > 0.001). Conclusion Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.

Acute limb ischemia caused by femoral arterial line induces remote liver injury in a rabbit model of liver ischemia/reperfusion injury.

Abstract: Femoral arterial lines are used for continuous monitoring of arterial blood pressure in experimental studies. However, placement of a catheter in the femoral artery could produce acute limb ischemia with associated systemic effects. The aim of this study was to investigate the effect of femoral arterial line insertion on liver function, in a rabbit liver lobar ischemia-reperfusion (I/R) model. Four groups of animals (n = 6 each) were studied: groups 1 and 2 (sham) underwent laparotomy but no liver ischemia. In groups 3 and 4 (I/R), liver lobar ischemia was induced for 60 minutes followed by 7 hours of reperfusion. In groups 1 and 3, the arterial line was placed in the femoral artery whereas in groups 2 and 4 in the ear artery. Liver function was assessed by serum alanine aminotransferase (ALT) activity, bile flow, plasma lactate levels, and histology. Results are expressed as mean +/- SEM. Alanine aminotransferase activity and lactate levels were significantly higher in the I/R femoral line group compared with the I/R ear line group at 7 hours postreperfusion. Bile production was significantly lower (75 +/- 9.6 vs 112 +/- 10 microL/min per 100 g liver weight). Histopathology showed more extensive hepatocellular necrosis and neutrophil accumulation in the I/R femoral line group compared with I/R ear line group. The sham femoral group showed liver injury, which was more marked than the ear line group (all P < .05). In conclusion, femoral artery cannulation induces remote liver injury. The use of femoral arterial lines should be avoided in experimental studies concerning liver function.

Anticoagulation after liver transplantation: a retrospective audit and case–control study

Abstract: Anticoagulation may in the future become a therapeutic option for the prevention of liver fibrosis, such as due to recurrent hepatitis C virus infection after liver transplantation. Currently, there are other indications for anticoagulation after liver transplantation but no data regarding its safety. The objective of the study was to audit the safety of anticoagulation after liver transplantation. Liver transplant recipients receiving anticoagulation postoperatively were compared with a matched control group with respect to bleeding complications and postoperative course. Anticoagulation did not increase the risk of bleeding complications after liver transplantation. On the basis of safety, it appears feasible to use anticoagulation in trials to assess prevention of liver fibrosis.

Authors' reply: Systematic review of randomized controlled trials on the effectiveness of virtual reality training for laparoscopic surgery (Br J Surg 2008; 95: 1088–1097)

Abstract: recent Darzi report1 to see that patientrelated outcomes, and quality of life in particular, are likely to become more dominant within our clinical practice. We believe that as our understanding of this type of data increases, so too will their clinical applications. Mr Lee is right to raise concerns about the length of time needed after surgery for some groups of colorectal cancer patients to resolve issues with respect to their quality of life. Addressing the psychosocial needs of patients is of paramount importance to those with incurable cancer, but as our work (confined to patients with potentially curable disease) shows, other groups of patients might also benefit from accessing similar services. Younger patients and those with stomas or low rectal anastomoses were identified as more likely to report lower than expected quality of life. More focused quality of life assessment, with psychosocial support offered appropriately, may help to minimize the impact of colorectal cancer and its treatment on the lives of these patients and their families. The wider use of quality of life data will inevitably help to identify vulnerable patients and guide appropriate intervention. T. R. Wilson and D. J. Alexander York Hospital, Wigginton Road, York YO31 8HE, UK DOI: 10.1002/bjs.6564