The White-test helps to reduce biliary leakage in liver resection: a systematic review and meta-analysis
Richard Linke, Frank Ulrich, Wolf O. Bechstein, Andreas A. Schnitzbauer
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Frankfurt University Hospitals, Goethe-University Frankfurt/Main, Department of General and Visceral Surgery, Frankfurt/Main, Germany
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Bechstein, Andreas A. Schnitzbauer" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Richard" "apellidos" => "Linke" ] 1 => array:2 [ "nombre" => "Frank" "apellidos" => "Ulrich" ] 2 => array:2 [ "nombre" => "Wolf O." "apellidos" => "Bechstein" ] 3 => array:4 [ "nombre" => "Andreas A." "apellidos" => "Schnitzbauer" "email" => array:1 [ 0 => "andreas.schnitzbauer@kgu.de" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Frankfurt University Hospitals, Goethe-University Frankfurt/Main, Department of General and Visceral Surgery, Frankfurt/Main, Germany" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 261 "Ancho" => 1046 "Tamanyo" => 43673 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Forest-plot (including Funnel-plot) of studies investigating the incidence of post-operative biliary leakage when using the White-test.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatic surgery is one of the most challenging surgical procedures due to its anatomical and pathophysiologic varieties and features.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Once a resection has been performed, various problems can complicate the post-operative course. One of the major contributors to morbidity is the occurrence of biliary leakages which is present in up to 30% of patients after hepatic surgical procedures.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Intraoperative bile leakage testing is one of the methods to prevent or at least reduce the incidence of postoperatively occurring bile leaks. The White-test seems to be the most promising test. In brief, a cannula is inserted in either the cystic duct after cholecystectomy or the common bile duct or right or left hepatic duct (depending upon the procedure). A fatty emulsion (e.g. 5% fat content parenteral nutrition supplement) is injected with gentle pressure. In case of biliary leakage extravasation of fatty emulsion can be detected and the leak oversewn accordingly. The test can be repeated without contamination of the resection surface at the surgeon’s choice, because the fatty emulsion can easily be washed away with saline without leaving any color behind. Various reports implicate the usefulness of the White-Test in the detection and reduction of biliary leakage.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Moreover, a recent meta-analysis investigating various intraoperative biliary leakage testing by Wang, <span class="elsevierStyleItalic">et al.</span> revealed superiority of the White-test <span class="elsevierStyleItalic">vs.</span> other tests like application of methylene-blue and others.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> We thus performed a systematic review with validation of the existing evidence for the White-test <span class="elsevierStyleItalic">vs.</span> no intraoperative testing. The investigation of the potentially best intraoperative biliary leakage test should serve as hypothesis driving analysis for high-quality randomized controlled trials in the future.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Systematic literature search</span><p id="p0010" class="elsevierStylePara elsevierViewall">Databases (Cochrane, PICO-search, pubmed.com, EMBASE and google.scholar) were screened for studies investigating the White-Test during hepatic resection with the search terms “White-Test”, “biliary leakage”, “bile leakage”, “bile leakage test”, and “biliary leakage test”. The search was performed for all years available ending in February 2014 to include the most recent manuscripts. Only publications in German and English language investigating the White-test (alternatively referred to as fatty-emulsion test) were included in the review and meta-analysis. Two authors (RL and AAS) reviewed the manuscripts for suitability (duplicate review) and only if both gave a positive vote, the manuscript was included in the analysis. In case of conflicts were observed, a third author (FU) was asked for suitability and the decision of in- or exclusion based on a simple majority.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Inclusion and exclusion criteria</span><p id="p0015" class="elsevierStylePara elsevierViewall">The primary aim was to include randomized controlled trials, large cohort-studies investigating the White-test <span class="elsevierStyleItalic">vs.</span> no intraoperative biliary leakage test or at least well-matched case-controlled studies into this systematic review and meta-analysis. Additionally, our original data of a cohort-study with 125 patients were included in this analysis. Patients should undergo elective hepatic surgery. All trials investigating biliary-leakage tests other than the White-test (e.g. saline-application, or methyleneblue application or indocyanine-green application) were excluded from the analysis.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Primary and secondary outcome measure</span><p id="p0020" class="elsevierStylePara elsevierViewall">A primary comparison was made for the incidence of post-operative biliary leakages after White-testing <span class="elsevierStyleItalic">vs.</span> no specific testing during hepatic surgery. Secondary outcome measure was a positive finding of intraoperative biliary leakages after White-testing <span class="elsevierStyleItalic">vs.</span> no specific testing.</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Assessment of quality of included studies</span><p id="p0025" class="elsevierStylePara elsevierViewall">The analyzed manuscripts did not undergo specific quality assessment with Jadad-scoring for randomized controlled trials, or the Newcastle-Ottawa score for non-randomized trials due to a broad noncompliance and hazard of unregistered clinical trials to these statements.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Instead we performed a critical review of evidence levels, which led to considerably lower evidence levels and classified evidence in the particular included trials in accordance with the definition of evidence of the Centre of Evidence in Medicine as outlined in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Moreover the methodological quality of each included study was assessed using the questions outlined in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>.</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Analysis of the incidence of biliary leakage with and without White-test in our center</span><p id="p0030" class="elsevierStylePara elsevierViewall">An analysis of 125 consecutive cases of major hepatic resections in accordance with the Brisbane classification (> 3 segments) carried out at Frankfurt University Clinic between 2011 and 2012 was performed.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Groups were divided into patients undergoing resection in which an intraoperative White-test was applied and in those that did not receive a White-test routinely during operation. Patient data included performance of White-test, intraoperative identification of biliary leakages and the postoperative incidence of biliary leakage in accordance with the definition of the International Study Group for Liver Surgery (ISGLS).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Data were included in the meta-analysis.</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Statistical analysis and data extraction</span><p id="p0035" class="elsevierStylePara elsevierViewall">Data investigating the primary and secondary outcome measures of the selected publications were collected as total numbers from the original publications. The dichotomous outcomes were arranged in fourfold-tables for each independent study. Using the Mantel-Haenszel method assuming a fixed effects model an analysis of pooled data was performed. Odds Ratios of the meta-analysis were displayed with 95% confidence intervals (95% CI) in Forest plots. Analyses were performed with Review Manager (RevMan), version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.</p></span></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Results</span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Results of the literature search</span><p id="p0040" class="elsevierStylePara elsevierViewall">With the preferred terms used we identified 1,630 articles. After removal of duplicates, 1,116 articles remained, of which 42 investigated the intraoperative use of biliary leakage testing. Removal of those not investigating the White-test (introduced in 2006 by the Essen-group of Silvio Nadalin<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>) and reviews led to a total of 3 studies plus our own data which were suitable for analysis of primary and secondary outcome measure. For the analysis of primary and secondary outcome 4 studies were included. Notably, 1 study was only included in the secondary outcome analysis, and our own data were included both analyses. The selection diagram of the PRISMA-statement is elaborated in <a class="elsevierStyleCrossRef" href="#f0005">figure 1</a>.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Included studies</span><p id="p0045" class="elsevierStylePara elsevierViewall">For the primary outcome measure “incidence of postoperative biliary leakage” 3 studies (including our original data) were chosen. Li, <span class="elsevierStyleItalic">et al.</span> originally described the method in 2009. They performed an unmatched cohort study of two consecutive cohorts of patients in which the incidence of biliary leakage was determined intra-operatively and after operation.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Patients were not randomized. Liu, <span class="elsevierStyleItalic">et al.</span> performed a randomized controlled trial of Whitetest <span class="elsevierStyleItalic">vs.</span> No test describing a simple randomization procedure according to the admission sequence. Both, major and minor hepatectomies were included. Unfortunately, no adequate power calculation for sample size was provided.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Finally, data from a cohort of consecutive 125 patients undergoing major hepatectomies at our center were included in the analysis. White-test was performed at the discretion of the surgeon and not systematically applied in the investigated area. We only included data in the White-test group, which could be undoubtedly identified from surgical protocols and reports. For secondary outcome measure, the 3 mentioned studies were included. Additionally, a study performed by Leelawat, <span class="elsevierStyleItalic">et al.</span> was chosen which showed, that by testing with saline intraoperatively first, followed by White-testing in the same patients, a larger number of patients with intraoperative biliary leakage could be identified.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In total 369 patients (148 in the White-test and 221 in the No test group) were included in the primary outcome measure analysis. There was a statistically highly significant difference favoring White-Testing during hepatectomy to reduce the incidence of postoperative biliary leakage [OR: 0.30 (95% CI: 0.14; 0.63]; p = 0.002). The secondary outcome measure showed also a superiority of White-testing in comparison to no testing, respectively saline testing in one study [OR: 0.03 (95% CI: 0.02; 0.07]; p < 0.00001). Basic data of included studies are displayed in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>. Forest-plots of primary and secondary outcome measures are displayed in <a class="elsevierStyleCrossRefs" href="#f0010">figures 2</a>-<a class="elsevierStyleCrossRef" href="#f0025"><span class="elsevierStyleSup">5</span></a>.</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="f0020"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Excluded studies</span><p id="p0050" class="elsevierStylePara elsevierViewall">Excluded were studies that did not use an intraoperative biliary leakage test and studies that tested other biliary leakage tests without using the White-test, like solely application of methylene-blue, indocyanine-green application, saline-application and others). Since the White-test is a recently introduced technique in hepatic surgery the number of analyzed studies was low including non-randomized cohort trials.</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Quality assessment and risk of bias</span><p id="p0055" class="elsevierStylePara elsevierViewall">The overall quality of existing evidence is medium to low. There was only one randomized controlled trial (RCT), however sample-size was not based on a statistical power-calculation. The other studies included were cohort-studies of acceptable size and a clear definition of treatment and control groups. Based on the definition of evidence levels provided by the Centre of Evidence in Oxford, all included studies including the low quality RCT must be classified as evidence level 2b: individual cohort-study (including low-quality RCT).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Risk of bias was assessed according to the guidelines of the Cochrane Group (Cochrane Handbook Version 5.1.0, section 8). As there are no randomized controlled trials, one must assume a relatively high risk of bias throughout the studies. This accounts particularly for the selection of the treatment modality. There was no blinding for data assessment described, so detection bias can be at high risk. The lack of published study protocols in advance precludes exclusion of selective outcome reporting. Moreover, a quality assessment of study performance cofounders was performed and outlined in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>. This assessment detects an overall low quality of the performed studies.</p></span></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Discussion</span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Summary of main results</span><p id="p0060" class="elsevierStylePara elsevierViewall">The White-Test for the identification of biliary leakages intraoperatively and the reduction of the incidence of postoperative biliary leakage showed a significant reduction in the incidence of postoperative biliary leakage [OR 0.30 (95% CI: 0.14, 0.63); p = 0.002]. The test is very good in detecting intraoperative biliary leakage due to its easy repeatability. It is superior to simple observation of the resection surface [OR 0.03 (95%CI: 0.02, 0.07); p < 0.00001].</p></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Overall completeness and applicability of evidence</span><p id="p0065" class="elsevierStylePara elsevierViewall">The findings of this systematic review and meta-analysis of White-test application during hepatic surgery to detect biliary leakage and thus reduce the incidence of post-hepatectomy biliary leakage are relevant for a better outcome in hepatobiliary surgery. Biliary leakage, with reported rates of up to 30% after major hepatectomy, special indications or complicated segmentectomies and atypical resections is one of the major contributor to morbidity in hepatobiliary surgery.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The test is easily to perform during surgery, cheap and repeatable at the surgeon’s choice. Therefore, cost-benefit estimation supports the use of the test during hepatic surgery.</p></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Quality of evidence</span><p id="p0070" class="elsevierStylePara elsevierViewall">The overall quality of evidence is at a medium level as outlined in the results section, which has some implication on future research, which will be outlined in the conclusion section. However, quality of the included studies was overall low: first, there is only one trial that performed a low quality randomization procedure. Second, 3 out of 4 analyzed studies were cohort studies, which limits the power of the findings significantly.</p></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Agreements and disagreements with other studies or reviews</span><p id="p0075" class="elsevierStylePara elsevierViewall">Currently, Wang, <span class="elsevierStyleItalic">et al.</span> published a review and meta-analysis of all available bile leakage tests.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The findings were similar and pointing out that the White-test is the best choice for the test when performed. A problematic aspect which is in disagreement with our review is the classification of evidence following proposed scoring systems for classification of publications.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The quality of some publications thus is overestimated and may have some suggestive effects on the uncritical reader. However, the White-Test seems to be the most promising tool to detect biliary leakage intraoperatively and avoid postoperative bile leakage in the conglomeration of low evidence. Therefore, our findings may be regarded as promising.</p></span></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Conclusions</span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Implications for practice</span><p id="p0080" class="elsevierStylePara elsevierViewall">Currently, there is one RCT investigating Whitetesting during hepatic surgery delivering promising results, which are confirmed by the findings of cohort-studies. White-test should be performed during hepatic surgery to detect biliary leakages and reduce the incidence of post-hepatectomy biliary leakage.</p></span><span id="s0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Implications for research</span><p id="p0085" class="elsevierStylePara elsevierViewall">For the future a RCT with adequate sample-size calculations is necessary to create solid evidence for the White-test. We are currently working on a protocol for a randomized controlled trial in hepatic surgery of White-test <span class="elsevierStyleItalic">vs.</span> No test after hepatic surgery to reduce the incidence of biliary leakage to increase quality in hepatobiliary surgery. As outlined in the current health strategy of the German government, only the increase of high-quality medical performance, which includes removal of medical insecurities, will help to improve care for our patients.</p></span></span><span id="s0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Author’S Contributions</span><p id="p0090" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">•</span><p id="p0095" class="elsevierStylePara elsevierViewall">RL: performed literature search, collected data and wrote parts oft he manuscript.</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0100" class="elsevierStylePara elsevierViewall">FU: generated idea and gave significant intellectual input.</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0105" class="elsevierStylePara elsevierViewall">WOB: generated idea and gave significant intellectual input.</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0110" class="elsevierStylePara elsevierViewall">AAS: generated idea, performed literature research and analysis and wrote parts of the manuscript.</p></li></ul></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1198574" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1117068" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Systematic literature search" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Inclusion and exclusion criteria" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Primary and secondary outcome measure" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Assessment of quality of included studies" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Analysis of the incidence of biliary leakage with and without White-test in our center" ] 5 => array:2 [ "identificador" => "s0040" "titulo" => "Statistical analysis and data extraction" ] ] ] 4 => array:3 [ "identificador" => "s0045" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "s0050" "titulo" => "Results of the literature search" ] 1 => array:2 [ "identificador" => "s0055" "titulo" => "Included studies" ] 2 => array:2 [ "identificador" => "s0060" "titulo" => "Excluded studies" ] 3 => array:2 [ "identificador" => "s0065" "titulo" => "Quality assessment and risk of bias" ] ] ] 5 => array:3 [ "identificador" => "s0070" "titulo" => "Discussion" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "s0075" "titulo" => "Summary of main results" ] 1 => array:2 [ "identificador" => "s0080" "titulo" => "Overall completeness and applicability of evidence" ] 2 => array:2 [ "identificador" => "s0085" "titulo" => "Quality of evidence" ] 3 => array:2 [ "identificador" => "s0090" "titulo" => "Agreements and disagreements with other studies or reviews" ] ] ] 6 => array:3 [ "identificador" => "s0095" "titulo" => "Conclusions" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "s0100" "titulo" => "Implications for practice" ] 1 => array:2 [ "identificador" => "s0105" "titulo" => "Implications for research" ] ] ] 7 => array:2 [ "identificador" => "s0110" "titulo" => "Author’S Contributions" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-04-01" "fechaAceptado" => "2014-10-06" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1117068" "palabras" => array:3 [ 0 => "Diagnostic dye" 1 => "Intraoperative test" 2 => "Lipid solution" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Background.</span> Bile leakage testing may help to detect and reduce the incidence of biliary leakage after hepatic resection. This review was performed to investigate the value of the White-test in identifying intraoperative biliary leakage and avoiding postoperative leakage.</p><p id="sp1040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods.</span> A systematic review and meta-analysis was performed. Two researchers performed literature research. Primary outcome measure was the incidence of post-hepatectomy biliary leakage; secondary outcome measure was the ability of detecting intraoperative biliary leakage with the help of the White-test.</p><p id="sp2040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results.</span> A total of 4 publications (including original data from our center) were included in the analysis. Evidence levels of the included studies had medium quality of 2b (individual cohort studies including low quality randomized controlled trials). Use of the White-test led to a significant reduction of post-operative biliary leakage [OR: 0.3 (95% CI: 0.14, 0.63), p = 0.002] and led to a significant higher intraoperative detection of biliary leakages [OR: 0.03 (95%CI: 0.02, 0.07), p < 0.00001].</p><p id="sp4040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusion.</span> Existing evidence implicates the use of the White-test after hepatic resection to identify bile leaks intraoperatively and thus reduce incidence of post-operative biliary leakage. Nonetheless, there is a requirement for a high-quality randomized controlled trial with adequately powered sample-size to confirm findings from the above described studies and further increase evidence in this field.</p></span>" ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 534 "Ancho" => 1043 "Tamanyo" => 68409 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Prisma-statement for selection of included trials. Notably, 3 studies included are published, one study* contains data from our center which were included in the analysis.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 261 "Ancho" => 1046 "Tamanyo" => 43673 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Forest-plot (including Funnel-plot) of studies investigating the incidence of post-operative biliary leakage when using the White-test.</p>" ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 337 "Ancho" => 503 "Tamanyo" => 11590 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Figure 3.</p>" ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 284 "Ancho" => 1046 "Tamanyo" => 49359 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Forest-plot (including Funnel-plot) of studies investigating the incidence of intraoperative detection of biliary leakage when using the White-Test.</p>" ] ] 4 => array:7 [ "identificador" => "f0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 341 "Ancho" => 503 "Tamanyo" => 10139 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Figure 5.</p>" ] ] 5 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Design/Evidence level \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparison \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Li, <span class="elsevierStyleItalic">et al.</span> 2009<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Individual cohort-study/2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">White-test <span class="elsevierStyleItalic">vs.</span> No test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 <span class="elsevierStyleItalic">vs.</span> 74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Germany \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liu, <span class="elsevierStyleItalic">et al.</span> 2012<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low quality RCT/2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">White-test <span class="elsevierStyleItalic">vs.</span> No test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 <span class="elsevierStyleItalic">vs.</span> 54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">China \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leelawat, <span class="elsevierStyleItalic">et al.</span> 2012<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Individual cohort-study/2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">White test + Saline test in the same group of patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thailand \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Linke, <span class="elsevierStyleItalic">et al.</span> 2014 Original data in this manuscript. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Individual cohort-study/2a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">White-test <span class="elsevierStyleItalic">vs.</span> No test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 <span class="elsevierStyleItalic">vs.</span> 93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Germany \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046975.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Basic data on included studies.</p>" ] ] 6 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">N: no. Y: yes. ?: unknown.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adequate sequence generation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Allocation concealment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Blinding \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incomplete outcome data addressed \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Free of selective reporting \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Free of baseline imbalance bias \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Free from early stopping bias \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Free from academic bias \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Free from sponsor bias \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Li, <span class="elsevierStyleItalic">et al.</span> 2009<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liu, <span class="elsevierStyleItalic">et al.</span> 2012<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leelawat, <span class="elsevierStyleItalic">et al.</span> 2012<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Linke, <span class="elsevierStyleItalic">et al.</span> 2014 Original data in this manuscript \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Y \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046976.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Quality assessment of studies included.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 10 | 4 | 14 |
| 2024 September | 39 | 9 | 48 |
| 2024 August | 25 | 6 | 31 |
| 2024 July | 25 | 2 | 27 |
| 2024 June | 14 | 4 | 18 |
| 2024 May | 24 | 3 | 27 |
| 2024 April | 16 | 1 | 17 |
| 2024 March | 36 | 8 | 44 |
| 2024 February | 25 | 4 | 29 |
| 2024 January | 14 | 5 | 19 |
| 2023 December | 10 | 6 | 16 |
| 2023 November | 21 | 4 | 25 |
| 2023 October | 46 | 1 | 47 |
| 2023 September | 14 | 3 | 17 |
| 2023 August | 15 | 1 | 16 |
| 2023 July | 8 | 1 | 9 |
| 2023 June | 38 | 4 | 42 |
| 2023 May | 52 | 0 | 52 |
| 2023 April | 66 | 0 | 66 |
| 2023 March | 34 | 1 | 35 |
| 2023 February | 22 | 5 | 27 |
| 2023 January | 5 | 2 | 7 |
| 2022 December | 14 | 7 | 21 |
| 2022 November | 24 | 7 | 31 |
| 2022 October | 18 | 4 | 22 |
| 2022 September | 10 | 5 | 15 |
| 2022 August | 10 | 5 | 15 |
| 2022 July | 22 | 5 | 27 |
| 2022 June | 11 | 6 | 17 |
| 2022 May | 16 | 6 | 22 |
| 2022 April | 18 | 6 | 24 |
| 2022 March | 11 | 9 | 20 |
| 2022 February | 16 | 5 | 21 |
| 2022 January | 38 | 3 | 41 |
| 2021 December | 21 | 6 | 27 |
| 2021 November | 27 | 7 | 34 |
| 2021 October | 33 | 10 | 43 |
| 2021 September | 23 | 7 | 30 |
| 2021 August | 17 | 7 | 24 |
| 2021 July | 22 | 9 | 31 |
| 2021 June | 16 | 8 | 24 |
| 2021 May | 16 | 6 | 22 |
| 2021 April | 20 | 15 | 35 |
| 2021 March | 55 | 5 | 60 |
| 2021 February | 4 | 7 | 11 |
| 2021 January | 9 | 6 | 15 |
| 2020 December | 6 | 8 | 14 |
| 2020 November | 13 | 7 | 20 |
| 2020 October | 7 | 6 | 13 |
| 2020 September | 12 | 6 | 18 |
| 2020 August | 5 | 2 | 7 |
| 2020 July | 4 | 1 | 5 |
| 2020 June | 3 | 1 | 4 |
| 2020 May | 5 | 5 | 10 |
| 2020 April | 1 | 3 | 4 |
| 2020 March | 3 | 1 | 4 |
| 2020 February | 11 | 5 | 16 |
| 2020 January | 7 | 1 | 8 |
| 2019 December | 10 | 8 | 18 |
| 2019 November | 4 | 0 | 4 |
| 2019 October | 0 | 2 | 2 |
| 2019 September | 2 | 1 | 3 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 1 | 6 | 7 |
| 2019 June | 8 | 6 | 14 |
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