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Showing papers by "Brian R. Davidson published in 2015"


Journal ArticleDOI
TL;DR: Complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture is demonstrated, a key advance in bioartificial liver development.
Abstract: Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.

329 citations


Journal ArticleDOI
TL;DR: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate, and further evidence for treatment effectiveness is required for ALD and NAFLD.
Abstract: BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

140 citations


Journal ArticleDOI
TL;DR: The bivariate model was used to obtain pooled estimates of sensitivity and specificity and there was no evidence of a difference in sensitivity or specificity between EUS and MRCP.
Abstract: Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are tests used in the diagnosis of common bile duct stones in patients suspected of having common bile duct stones prior to undergoing invasive treatment. There has been no systematic review of the accuracy of EUS and MRCP in the diagnosis of common bile duct stones using appropriate reference standards. Objectives were to determine and compare the accuracy of EUS and MRCP for the diagnosis of common bile duct stones. We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov until September 2012. We searched the references of included studies to identify further studies and of systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We included studies that provided the number of true positives, false positives, false negatives, and true negatives for EUS or MRCP. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct or symptom free follow-up for at least six months for a negative test, as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis ; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones ; and before or after cholecystectomy. At least two authors independently screened abstracts and selected studies for inclusion. Two authors independently collected the data from each study. We used the bivariate model to obtain pooled estimates of sensitivity and specificity. We included a total of 18 studies involving 2366 participants (976 participants with common bile duct stones and 1390 participants without common bile duct stones). Eleven studies evaluated EUS alone, and five studies evaluated MRCP alone. Two studies evaluated both tests. Most studies included patients who were suspected of having common bile duct stones based on abnormal liver function tests ; abnormal transabdominal ultrasound ; symptoms such as obstructive jaundice, cholangitis, or pancreatitis ; or a combination of the above. The proportion of participants who had undergone cholecystectomy varied across studies. Not one of the studies was of high methodological quality. For EUS, the sensitivities ranged between 0.75 and 1.00 and the specificities ranged between 0.85 and 1.00. The summary sensitivity (95% confidence interval (CI)) and specificity (95% CI) of the 13 studies that evaluated EUS (1537 participants ; 686 cases and 851 participants without common bile duct stones) were 0.95 (95% CI 0.91 to 0.97) and 0.97 (95% CI 0.94 to 0.99). For MRCP, the sensitivities ranged between 0.77 and 1.00 and the specificities ranged between 0.73 and 0.99. The summary sensitivity and specificity of the seven studies that evaluated MRCP (996 participants ; 361 cases and 635 participants without common bile duct stones) were 0.93 (95% CI 0.87 to 0.96) and 0.96 (95% CI 0.90 to 0.98). There was no evidence of a difference in sensitivity or specificity between EUS and MRCP (P value = 0.5). From the included studies, at the median pre-test probability of common bile duct stones of 41% the post-test probabilities (with 95% CI) associated with positive and negative EUS test results were 0.96 (95% CI 0.92 to 0.98) and 0.03 (95% CI 0.02 to 0.06). At the same pre-test probability, the post-test probabilities associated with positive and negative MRCP test results were 0.94 (95% CI 0.87 to 0.97) and 0.05 (95% CI 0.03 to 0.09). Both EUS and MRCP have high diagnostic accuracy for detection of common bile duct stones. People with positive EUS or MRCP should undergo endoscopic or surgical extraction of common bile duct stones and those with negative EUS or MRCP do not need further invasive tests. However, if the symptoms persist, further investigations will be indicated. The two tests are similar in terms of diagnostic accuracy and the choice of which test to use will be informed by availability and contra-indications to each test. However, it should be noted that the results are based on studies of poor methodological quality and so the results should be interpreted with caution. Further studies that are of high methodological quality are necessary to determine the diagnostic accuracy of EUS and MRCP for the diagnosis of common bile duct stones.

136 citations


Journal ArticleDOI
TL;DR: Recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies.
Abstract: In 1993, Przyklenk and colleagues made the intriguing experimental observation that ‘brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion’ and that this effect ‘…. may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion’. This seminal study laid the foundation for the discovery of ‘remote ischemic conditioning’ (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit.

107 citations


Journal ArticleDOI
TL;DR: This study assessed ultrasound and reported higher sensitivities for bilirubin and alkaline phosphatase at both cut-offs but the specificities of the markers were higher at only the greater than twice the normal limit cut-off.
Abstract: Background Ultrasound and liver function tests (serum bilirubin and serum alkaline phosphatase) are used as screening tests for the diagnosis of common bile duct stones in people suspected of having common bile duct stones. There has been no systematic review of the diagnostic accuracy of ultrasound and liver function tests. Objectives To determine and compare the accuracy of ultrasound versus liver function tests for the diagnosis of common bile duct stones. Search methods We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov to September 2012. We searched the references of included studies to identify further studies and systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects, Health Technology Assessment, Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. Selection criteria We included studies that provided the number of true positives, false positives, false negatives, and true negatives for ultrasound, serum bilirubin, or serum alkaline phosphatase. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test result, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct, or symptom-free follow-up for at least six months for a negative test result as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors screened abstracts and selected studies for inclusion independently. Data collection and analysis Two authors independently collected data from each study. Where meta-analysis was possible, we used the bivariate model to summarise sensitivity and specificity. Main results Five studies including 523 participants reported the diagnostic accuracy of ultrasound. One studies (262 participants) compared the accuracy of ultrasound, serum bilirubin and serum alkaline phosphatase in the same participants. All the studies included people with symptoms. One study included only participants without previous cholecystectomy but this information was not available from the remaining studies. All the studies were of poor methodological quality. The sensitivities for ultrasound ranged from 0.32 to 1.00, and the specificities ranged from 0.77 to 0.97. The summary sensitivity was 0.73 (95% CI 0.44 to 0.90) and the specificity was 0.91 (95% CI 0.84 to 0.95). At the median pre-test probability of common bile duct stones of 0.408, the post-test probability (95% CI) associated with positive ultrasound tests was 0.85 (95% CI 0.75 to 0.91), and negative ultrasound tests was 0.17 (95% CI 0.08 to 0.33). The single study of liver function tests reported diagnostic accuracy at two cut-offs for bilirubin (greater than 22.23 μmol/L and greater than twice the normal limit) and two cut-offs for alkaline phosphatase (greater than 125 IU/L and greater than twice the normal limit). This study also assessed ultrasound and reported higher sensitivities for bilirubin and alkaline phosphatase at both cut-offs but the specificities of the markers were higher at only the greater than twice the normal limit cut-off. The sensitivity for ultrasound was 0.32 (95% CI 0.15 to 0.54), bilirubin (cut-off greater than 22.23 μmol/L) was 0.84 (95% CI 0.64 to 0.95), and alkaline phosphatase (cut-off greater than 125 IU/L) was 0.92 (95% CI 0.74 to 0.99). The specificity for ultrasound was 0.95 (95% CI 0.91 to 0.97), bilirubin (cut-off greater than 22.23 μmol/L) was 0.91 (95% CI 0.86 to 0.94), and alkaline phosphatase (cut-off greater than 125 IU/L) was 0.79 (95% CI 0.74 to 0.84). No study reported the diagnostic accuracy of a combination of bilirubin and alkaline phosphatase, or combinations with ultrasound. Authors' conclusions Many people may have common bile duct stones in spite of having a negative ultrasound or liver function test. Such people may have to be re-tested with other modalities if the clinical suspicion of common bile duct stones is very high because of their symptoms. False-positive results are also possible and further non-invasive testing is recommended to confirm common bile duct stones to avoid the risks of invasive testing. It should be noted that these results were based on few studies of poor methodological quality and the results for ultrasound varied considerably between studies. Therefore, the results should be interpreted with caution. Further studies of high methodological quality are necessary to determine the diagnostic accuracy of ultrasound and liver function tests.

87 citations



Journal ArticleDOI
TL;DR: Factors influencing long‐term outcome after surgical resection for duodenal adenocarcinoma are unclear.
Abstract: BackgroundFactors influencing long‐term outcome after surgical resection for duodenal adenocarcinoma are unclear.MethodsA prospectively created database was reviewed for patients undergoing surgery for duodenal adenocarcinoma in six UK hepatopancreaticobiliary centres from 2000 to 2013. Factors influencing overall survival and disease‐free survival (DFS) were identified by regression analysis.ResultsResection with curative intent was performed in 150 (84·3 per cent) of 178 patients. The postoperative morbidity rate for these patients was 40·0 per cent and the in‐hospital mortality rate was 3·3 per cent. Patients who underwent resection had a better median survival than those who had a palliative surgical procedure (84 versus 8 months; P < 0·001). The 1‐, 3‐ and 5‐year overall survival rates for patients who underwent resection were 83·9, 66·7 and 51·2 per cent respectively. Median DFS was 53 months, and 1‐ and 3‐year DFS rates were 80·8 and 56·5 per cent respectively. Multivariable analysis revealed that node status (hazard ratio 1·73, 95 per cent c.i. 1·07 to 2·79; P = 0·006) and lymphovascular invasion (hazard ratio 3·49, 1·83 to 6·64; P = 0·003) were associated with overall survival.ConclusionResection of duodenal adenocarcinoma in specialist centres is associated with good long‐term survival. Lymphovascular invasion and nodal metastases are independent prognostic indicators.

49 citations


Journal ArticleDOI
TL;DR: Exome sequencing of sporadic pancreatic neuroendocrine tumours has identified mutually exclusive mutations in the chromatin regulators α- thalassaemia/mental retardation X-linked (ATRX) and death associated protein 6 (DAXX) genes in 43% of cases.
Abstract: Exome sequencing of sporadic pancreatic neuroendocrine tumours (PNETs) has identified mutually exclusive mutations in the chromatin regulators α- thalassaemia/mental retardation X-linked (ATRX) and death associated protein 6 (DAXX) genes in 43% of cases (18% and 23% of cases respectively in 68 cases studied) (Elsasser et al. 2011; Jiao et al. 2011). ATRX and DAXX are chromatin remodelers; their loss leads to alternative lengthening of telomeres (ALT) and chromosomal instability (CIN) (Heaphy et al. 2011). ALT is a telomerase independent mechanism for maintenance of telomere stabilisation. Although it was initially reported that ATRX/DAXX mutant tumours had superior 10-year survival and outcome (Jiao et al. 2011), a recent larger study on 243 tumours has demonstrated that ATRX and DAXX loss and associated ALT in PNETs correlates with CIN, advanced tumour stage, development of metastases and poorer progression free (PFS) and overall survival (OS) (Marinoni et al. 2014) ...

48 citations


Proceedings ArticleDOI
TL;DR: An analysis of the registration component of a proposed image guidance system for image guided liver surgery, using contrast enhanced CT, shows that registration can be performed during surgery, with an error of less than 10 mm RMS for multiple surface landmarks.
Abstract: We present an analysis of the registration component of a proposed image guidance system for image guided liver surgery, using contrast enhanced CT The analysis is performed on a visually realistic liver phantom and in-vivo porcine data A robust registration process that can be deployed clinically is a key component of any image guided surgery system It is also essential that the accuracy of the registration can be quantified and communicated to the surgeon We summarise the proposed guidance system and discuss its clinical feasibility The registration combines an intuitive manual alignment stage, surface reconstruction from a tracked stereo laparoscope and a rigid iterative closest point registration to register the intra-operative liver surface to the liver surface derived from CT Testing of the system on a liver phantom shows that subsurface landmarks can be localised to an accuracy of 29 mm RMS Testing during five porcine liver surgeries demonstrated that registration can be performed during surgery, with an error of less than 10 mm RMS for multiple surface landmarks

45 citations


Journal ArticleDOI
TL;DR: The bivariate model was used to summarise the sensitivity and specificity of the tests and identified five studies including 318 participants and five studies that reported the diagnostic accuracy of ERCP and IOC that were of high methodological quality.
Abstract: Background Endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography (IOC) are tests used in the diagnosis of common bile duct stones in people suspected of having common bile duct stones. There has been no systematic review of the diagnostic accuracy of ERCP and IOC. Objectives To determine and compare the accuracy of ERCP and IOC for the diagnosis of common bile duct stones. Search methods We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov to September 2012. To identify additional studies, we searched the references of included studies and systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects (DARE)), Health Technology Assessment (HTA), Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. Selection criteria We included studies that provided the number of true positives, false positives, false negatives, and true negatives for ERCP or IOC. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct, or symptom-free follow-up for at least six months for a negative test as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones; with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors screened abstracts and selected studies for inclusion independently. Data collection and analysis Two authors independently collected data from each study. We used the bivariate model to summarise the sensitivity and specificity of the tests. Main results We identified five studies including 318 participants (180 participants with and 138 participants without common bile duct stones) that reported the diagnostic accuracy of ERCP and five studies including 654 participants (125 participants with and 529 participants without common bile duct stones) that reported the diagnostic accuracy of IOC. Most studies included people with symptoms (participants with jaundice or pancreatitis) suspected of having common bile duct stones based on blood tests, ultrasound, or both, prior to the performance of ERCP or IOC. Most studies included participants who had not previously undergone removal of the gallbladder (cholecystectomy). None of the included studies was of high methodological quality as evaluated by the QUADAS-2 tool (quality assessment tool for diagnostic accuracy studies). The sensitivities of ERCP ranged between 0.67 and 0.94 and the specificities ranged between 0.92 and 1.00. For ERCP, the summary sensitivity was 0.83 (95% confidence interval (CI) 0.72 to 0.90) and specificity was 0.99 (95% CI 0.94 to 1.00). The sensitivities of IOC ranged between 0.75 and 1.00 and the specificities ranged between 0.96 and 1.00. For IOC, the summary sensitivity was 0.99 (95% CI 0.83 to 1.00) and specificity was 0.99 (95% CI 0.95 to 1.00). For ERCP, at the median pre-test probability of common bile duct stones of 0.35 estimated from the included studies (i.e., 35% of people suspected of having common bile duct stones were confirmed to have gallstones by the reference standard), the post-test probabilities associated with positive test results was 0.97 (95% CI 0.88 to 0.99) and negative test results was 0.09 (95% CI 0.05 to 0.14). For IOC, at the median pre-test probability of common bile duct stones of 0.35, the post-test probabilities associated with positive test results was 0.98 (95% CI 0.85 to 1.00) and negative test results was 0.01 (95% CI 0.00 to 0.10). There was weak evidence of a difference in sensitivity (P value = 0.05) with IOC showing higher sensitivity than ERCP. There was no evidence of a difference in specificity (P value = 0.7) with both tests having similar specificity. Authors' conclusions Although the sensitivity of IOC appeared to be better than that of ERCP, this finding may be unreliable because none of the studies compared both tests in the same study populations and most of the studies were methodologically flawed. It appears that both tests were fairly accurate in guiding further invasive treatment as most people diagnosed with common bile duct stones by these tests had common bile duct stones. Some people may have common bile duct stones in spite of having a negative ERCP or IOC result. Such people may have to be re-tested if the clinical suspicion of common bile duct stones is very high because of their symptoms or persistently abnormal liver function tests. However, the results should be interpreted with caution given the limited quantity and quality of the evidence.

45 citations


Journal ArticleDOI
TL;DR: This review evaluated the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection.
Abstract: Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure.The surgeon covers the closed surgical wound with either a dressing or adhesive tape.The dressing can act as a physical barrier to protect the wound until the continuity of the skin in restored (within about 48 hours). It can also absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that it is a disadvantage, as excessive exudate can cause softening and deterioration of the wound and surrounding healthy tissue. The authors reviewed the medical literature up to July 2013 and identified four randomised controlled trials that investigated early (permanent removal of dressings within 48 hours of surgery) versus delayed removal of dressings (permanent removal of dressings after 48 hours of surgery with interim changes of dressing allowed) in people with surgical wounds. The levels of bias across the studies were mostly high or unclear, i.e. flaws in the conduct of these trials could have resulted in the production of incorrect results. A total of 280 people undergoing planned surgery were included in this review. One-hundred and forty people had their dressings removed within 48 hours following surgery and 140 people had their wounds dressed beyond 48 hours. The choice of whether the dressing was removed early (within 48 hours) or retained for more 48 hours was made randomly by a method similar to the toss of a coin. No significant differences were reported between the two groups in terms of superficial surgical site infection (infection of the wound), superficial wound dehiscence (partial disruption of the wound that results in it reopening at the skin surface) or the number of people experiencing serious adverse events. There were no deep wound infections or complete wound dehiscence (complete disruption of wound healing, when the wound reopens completely) in the studies that reported these complications. However, the studies were not large enough to identify small differences in complication rates. None of the studies reported quality of life. Participants in the group that had early removal of dressings had significantly shorter hospital stays and incurred significantly lower treatment costs than those in the delayed removal of dressings group, but these results were based on very low quality evidence from one small randomised controlled trial. We recommend further randomised controlled trials are performed to investigate whether dressing of wounds beyond 48 hours after surgery is necessary, since the current evidence is based on very low quality evidence from three small randomised controlled trials.

Journal ArticleDOI
20 Jun 2015
TL;DR: A practical image-guided surgery system based on locally rigid registration of a CT-derived model to vascular structures located with LUS is proposed and accuracy of target location commensurate with surgical requirements is demonstrated.
Abstract: Purpose Laparoscopic liver resection has significant advantages over open surgery due to less patient trauma and faster recovery times, yet is difficult for most lesions due to the restricted field of view and lack of haptic feedback. Image guidance provides a potential solution but is challenging in a soft deforming organ such as the liver. In this paper, we therefore propose a laparoscopic ultrasound (LUS) image guidance system and study the feasibility of a locally rigid registration for laparoscopic liver surgery.

Journal ArticleDOI
TL;DR: This review considers all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed to compare the benefits and harms of early post-operative bathing or showering.
Abstract: Background Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. Objectives To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. Search methods We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). Selection criteria We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. Data collection and analysis We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. Main results Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. Authors' conclusions There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Journal ArticleDOI
23 Mar 2015-PLOS ONE
TL;DR: From the perspective of the UK NHS, MRCP was the most cost-effective test in the diagnosis of CBD stones.
Abstract: Patients with suspected common bile duct (CBD) stones are often diagnosed using endoscopic retrograde cholangiopancreatography (ERCP), an invasive procedure with risk of significant complications. Using endoscopic ultrasound (EUS) or Magnetic Resonance CholangioPancreatography (MRCP) first to detect CBD stones can reduce the risk of unnecessary procedures, cut complications and may save costs.

Journal ArticleDOI
TL;DR: Diagnostic laparoscopy prior to laparoscopic surgery in patients with CT-resectable cancer appears to be cost-effective in pancreatic cancer (but not in periampullary cancer), when laparotomy following diagnostic laparoscope occurs in a subsequent admission.
Abstract: Surgical resection is the only curative treatment for pancreatic and periampullary cancer, but many patients undergo unnecessary laparotomy because tumours can be understaged by computerised tomography (CT). A recent Cochrane review found diagnostic laparoscopy can decrease unnecessary laparotomy. We compared the cost-effectiveness of diagnostic laparoscopy prior to laparotomy versus direct laparotomy in patients with pancreatic and periampullary cancer with resectable disease based on CT scanning.

Journal ArticleDOI
TL;DR: There is not enough evidence to support the routine use of robotic surgery, single-incision laparoscopic cholecystectomy or natural orifice transluminal endoscopic surgery (NOTES) in the treatment of acute choleCystitis.
Abstract: Acute cholecystitis occurs in approximately 1 % of patients with known gallstones. It presents as a surgical emergency and usually requires hospitalisation for treatment. It is associated with significant morbidity and mortality, particularly in the elderly. Cholecystectomy is advocated for acute cholecystitis; however, the timing of cholecystectomy and the value of the additional treatments have been a matter of debate. This review examines the available evidence regarding the optimal surgical management of patients with acute cholecystitis. A literature search was performed on the MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform, databases for English language publications. The MeSH headings ‘cholecystitis’, ‘acute’, ‘gallbladder’, ‘inflammation’, ‘surgery’, ‘cholecystectomy’, ‘laparoscopic’, ‘robotic’, ‘telerobotic’ and ‘computer-assisted’ were used. Data from eight randomised controlled trails and three population-based analyses show that early cholecystectomy for acute cholecystitis performed on the index admission is safe and not associated with increased conversion rates or morbidity in comparison to conservative treatment followed by elective cholecystectomy. Delaying cholecystectomy increases readmissions for gallstone-related events, complications, hospital stay and mortality in the elderly. Early cholecystectomy is also more cost-effective. Randomised trials addressing antibiotic use in acute cholecystitis suggest that antibiotics should be stopped on the day of cholecystectomy. Insufficient trials have been performed to address the optimal analgesia regime post cholecystectomy. Similarly, a lack of trials on intraoperative cholangiography and management of common bile duct stones in patients with acute cholecystitis means that treatment of concomitant bile duct stones should be based on institutional expertise and resource availability. As regards acute cholecystitis in elderly and high-risk patients, case series and retrospective studies would suggest that cholecystectomy is more effective and of lower mortality than percutaneous cholecystostomy. There is not enough evidence to support the routine use of robotic surgery, single-incision laparoscopic cholecystectomy or natural orifice transluminal endoscopic surgery (NOTES) in the treatment of acute cholecystitis. Trial evidence would favour a policy of early laparoscopic cholecystectomy following admission with acute cholecystitis. The optimal approach to support early cholecystectomy is suggested but requires evidence from further randomised trials.

Book ChapterDOI
05 Oct 2015
TL;DR: The estimation of the shape and position of the liver after insufflation has many important applications, such as providing surface-based registration algorithms used in image guidance with an initial guess and realistic patient-specific surgical simulation.
Abstract: The insufflation of the abdomen in laparoscopic liver surgery leads to significant deformation of the liver The estimation of the shape and position of the liver after insufflation has many important applications, such as providing surface-based registration algorithms used in image guidance with an initial guess and realistic patient-specific surgical simulation

Journal ArticleDOI
TL;DR: Continuous vascular occlusion during hepatectomy results in decreased blood loss and decreased blood transfusion requirements.

Journal ArticleDOI
TL;DR: There are significant cost savings to be gained by avoiding routine PBD in patients with resectable pancreatic and periampullary cancer where PBD is still routinely used in this context; this economic evidence should be used to support the clinical argument for a change in practice.

Journal ArticleDOI
TL;DR: Primary hepatic leiomyoma (PHL) is an isolated pathology within the liver, without evidence of any other coexistingLeiomyomas, may occur in healthy individuals although an association with immunodeficiency and Epstein-Barr virus (EBV) infection has been observed.
Abstract: Leiomyomas are benign lesions arising from the smooth muscle layer. They are most commonly detected either within the gastrointestinal or genitourinary tracts. Primary hepatic leiomyoma (PHL) is a rare pathology. It is an isolated pathology within the liver, without evidence of any other coexisting leiomyomas. Very few cases have been described in literature. PHL may occur in healthy individuals although an association with immunodeficiency and Epstein-Barr virus (EBV) infection has been observed. Majority of the reported cases have been in females. A 20-year-old female patient presented with abdominal symptoms. MRI confirmed an 8 cm mass, with very low signal intensity on T2 images and peripheral rim enhancement on gadolinium. A laparoscopic left lateral sectorectomy was performed. Final histopathology confirmed the presence of benign lesion with spindle cell and smooth muscle proliferation and a fibro-vascular stroma compatible with a leiomyoma. There was no evidence of any leiomyomatous lesion elsewhere in the body. A rare diagnosis of PHL was therefore established. Acknowledging the rare incidence of this lesion, we report the same and review the relevant literature. PHL is usually a retrospective diagnosis, confirmed on histo-pathology assessment of the resected specimen. Liver resection is required in these patients due to the presence of symptoms, in the presence of a solid mass lesion within the liver. Surgery is thus definitive, diagnostic cum therapeutic.

Journal ArticleDOI
TL;DR: A valid risk prognostic model and a classification system of surgical complications are necessary before meaningful comparisons of the operative performance between pancreatic surgeons can be made.
Abstract: Background. Indicators of operative outcomes could be used to identify underperforming surgeons for support and training. The feasibility of identifying HPB surgeons with poor operative performance ("outliers") based on the results of pancreatic resections is not known. Methods. A systematic review of Medline, Embase, and the Cochrane library was performed to identify studies on pancreatic resection including at least 100 patients and published between 2004 and 2014. Proportions that lay outside the upper 95% and 99.8% confidence intervals based on results of the systematic reviews were considered as "outliers." Results. In total, 30 studies reporting on 10712 patients were eligible for inclusion in this review. The average short-term mortality after pancreatic resections was 3.1% and proportion of patients with procedure-related complications was 47.0%. None of the classification systems assessed the long-term impact of the complications on patients. The surgeon-specific mortality should be 5 times the average mortality before he or she can be identified as an outlier with 0.1% false positive rate if he or she performs 50 surgeries a year. Conclusions. A valid risk prognostic model and a classification system of surgical complications are necessary before meaningful comparisons of the operative performance between pancreatic surgeons can be made.

Journal ArticleDOI
TL;DR: A patient with a known diaphragmatic cyst presented with new onset right upper quadrant pain and Histology showed a benign epidermoid cyst, which was excised in view of symptoms and risk of neoplasia.
Abstract: Diaphragmatic lesions are usually congenital bronchogenic cysts. A patient with a known diaphragmatic cyst presented with new onset right upper quadrant pain. Repeat imaging showed enlargement of the cyst, the CA19-9 cancer marker was raised at 312 iu/ml (normal: <27 iu/ml) and positron emission tomography combined with computed tomography showed focally increased uptake in the cystic wall. In view of symptoms and risk of neoplasia, the lesion was excised. Histology showed a benign epidermoid cyst. Features falsely suggesting neoplasia have been reported previously with benign splenic cysts but not with a benign diaphragmatic epidermoid cyst.




Journal ArticleDOI
TL;DR: The experience of using a steerable intravascular catheter to guide a probe-based confocal laser endomicroscope is reported on the basis of a porcine model of laparoscopic liver resection.
Abstract: Probe-based confocal laser endomicroscopy is an emerging imaging modality that enables visualization of histologic details during endoscopy and surgery. A method of guiding the probe with millimeter accuracy is required to enable imaging in all regions of the abdomen accessed during laparoscopy. On the basis of a porcine model of laparoscopic liver resection, we report our experience of using a steerable intravascular catheter to guide a probe-based confocal laser endomicroscope.