Laparoscopic versus open liver resection for benign and malignant hepatic lesions in adults

  • Review
  • Intervention

Authors


Abstract

Background

Liver (hepatic) resection refers to removal of the whole liver, or one or more of its vascular segments. Elective liver resection is mainly performed for benign and malignant liver tumours. The operation can be performed as an open procedure or with a laparoscopic approach. With the advancement of laparoscopic skills and equipment, liver resection is selectively being carried out with this approach. A laparoscopic procedure is intended to be less severe, allowing for quicker healing, fewer complications, and a shorter hospital stay as the insult to the body is minimised. However, evidence about the efficacy of this approach when compared to an open procedure is still scattered. Current practice at different hepato-pancreato-biliary centres is based on the clinical judgement of experts in their field, which is highly insufficient in terms of evidence.

Objectives

To assess the benefits and harms of laparoscopic versus open liver resection for benign or malignant lesions on the liver in adult patients.

Search methods

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013. We also conducted searches of reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases.

Selection criteria

We searched for randomised clinical trials of participants undergoing liver resection for benign or malignant lesions which reported on benefits and harms. We searched for quasi-randomised or observational studies for reports of harm.

Data collection and analysis

No data from randomised clinical trials could be collected.

Main results

Two authors performed study selection independently. We were not able to identify any randomised clinical trials that met the inclusion criteria of our review protocol. We identified two ongoing randomised clinical trials performed in Europe with data yet to be published. We retrieved a few observational studies (prospective and retrospective) with the searches for randomised clinical trials. They included a limited number of participants in whom laparoscopic and open liver resection was compared. Since these studies were non-randomised observational studies, the results for any adverse events are not included in the review as the risk of bias in such studies is high.

Authors' conclusions

No conclusions can be made at this time as no randomised clinical trials are available. In addition to the two ongoing randomised clinical trials for which results are expected to be published in the near future, well-designed, prospective, randomised clinical trials are needed in order to evaluate the benefits and harms of the laparoscopic procedure versus open liver resection.

Résumé scientifique

Résection hépatique par laparoscopie contre chirurgie ouverte pour les lésions hépatiques bénignes et malignes chez l'adulte

Contexte

La résection hépatique (du foie) fait référence à l'ablation du foie entier, ou de l'un ou plusieurs de ses segments vasculaires. La résection hépatique élective est principalement pratiquée pour les tumeurs hépatiques bénignes et malignes. L'opération peut être réalisée par une procédure ouverte ou par une approche laparoscopique. Grâce aux progrès réalisés dans les techniques et l'équipement laparoscopiques, la résection hépatique est sélectivement pratiquée en appliquant cette approche. Une procédure laparoscopique est censée être moins grave, favorisant une cicatrisation plus rapide, un nombre réduit de complications, et une hospitalisation plus courte puisque le traumatisme subi par le corps est minimisé. Toutefois, les preuves en faveur de l'efficacité de cette approche comparée à une procédure effractive (ouverte) sont encore dispersées. La pratique actuelle dans différents centres de traitements hépato-pancréato-biliaires est fondée sur le jugement clinique des experts dans leur domaine, ce qui est très insuffisant en termes de preuves.

Objectifs

Évaluer les bénéfices et les risques de la résection hépatique par laparoscopie versus chirurgie ouverte pour les lésions bénignes et malignes du foie chez des patients adultes.

Stratégie de recherche documentaire

Nous avons effectué une recherche dans le registre des essais contrôlés du groupe Cochrane sur les affections hépato-biliaires, le registre Cochrane des essais contrôlés (CENTRAL) dans The Cochrane Library, MEDLINE, EMBASE et le Science Citation Index Expanded jusqu'à février 2013. Nous avons également recherché dans les bibliographies des articles pertinents et de revues, dans des actes de conférences et des bases de données d'essais en cours.

Critères de sélection

Nous avons cherché des essais contrôlés randomisés portant sur des participants subissant une résection hépatique pour des lésions bénignes ou malignes ayant rendu compte des bénéfices et des risques. Nous avons recherché des études quasi-randomisées ou observationnelles pour obtenir les comptes rendus sur les risques.

Recueil et analyse des données

Aucune donnée issue d'essais cliniques randomisés n'a pu être recueillie.

Résultats principaux

Deux auteurs ont effectué, de manière indépendante, la sélection des études. Nous ne sommes pas parvenus à identifier d'essai clinique randomisé remplissant les critères d'inclusion du protocole de notre revue. Nous avons identifié deux essais cliniques randomisés en cours de réalisation en Europe dont les données ne sont pas encore publiées. Nous avons trouvé quelques études observationnelles (prospectives et rétrospectives) lors des recherches d'essais cliniques randomisés. Elles avaient inclus un nombre limité de participants faisant l'objet de comparaisons de la résection hépatique par laparoscopie et par chirurgie ouverte. Comme ces études étaient des études observationnelles non randomisées, les résultats de tous les événements indésirables ne sont pas inclus dans la revue car le risque de biais dans de telles études est élevé.

Conclusions des auteurs

Aucune conclusion ne peut être émise à l'heure actuelle étant donné qu'il n'existe aucun essai clinique randomisé. Outre les deux essais cliniques randomisés en cours dont les résultats sont supposés être publiés très prochainement, des essais cliniques randomisés, prospectifs et bien conçus sont nécessaires pour évaluer les bénéfices et les risques de la résection hépatique par laparoscopie et par chirurgie ouverte.

Plain language summary

Laparoscopic versus open liver resection for benign and malignant hepatic lesions in adults

Conventionally, resection of benign and malignant liver lesions has been carried out using an open approach. This technique involves one long incision in the abdominal wall and removal of the lesion under direct vision. In the last two decades, laparoscopic surgery has gained the interest of surgeons, particularly in liver surgery, where resection of lesions is achieved using several small skin incisions in the abdominal wall and the operation is conducted under keyhole camera vision. This comparison of the efficacy and safety of both procedures for liver resection was inconclusive as there were no randomised clinical trials.

Résumé simplifié

Résection hépatique par laparoscopie contre chirurgie ouverte pour les lésions hépatiques bénignes et malignes chez l'adulte

De façon conventionnelle, la résection des lésions hépatiques bénignes et malignes est effectuée par chirurgie ouverte. Cette technique implique une incision longue dans la paroi abdominale et l'ablation de la lésion sous guidage direct par visualisation sur un écran vidéo. Au cours des deux dernières décennies, la chirurgie laparoscopique a attiré l'intérêt des chirurgiens, en particulier de la chirurgie du foie, au cours de laquelle la résection des lésions est réalisée en pratiquant plusieurs petites incisions cutanées dans la paroi abdominale et l'opération est conduite sous guidage par caméra minimalement invasive. Cette comparaison de l'efficacité et de la sécurité des deux procédures pour la résection hépatique n'a pas été concluante puisqu'il n'existe aucun essai clinique randomisé.

Notes de traduction

Traduit par: French Cochrane Centre 3rd June, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Background

Elective liver resection is carried out for the removal of benign and malignant lesions of the liver. The operation can be performed with minimally invasive surgery (laparoscopic) or as an open procedure. Since the introduction of laparoscopic liver surgery in 1990, more hepato-biliary centres are performing laparoscopic hepatic resection, particularly for specific types of segmental and benign lesions. This is based on the idea that the small multiple incisions used in laparoscopic surgery minimise the insult to the body and, hence, lead to better outcome and recovery for the patient.

Description of the condition

Liver lesions that require resection can be benign (non-cancerous) or malignant (cancerous). Common benign lesions of the liver are haemangiomas, hepatic adenomas, and focal nodular hyperplasia (Nichols 1989; Sherlock 2007). Haemangiomas are the most common benign liver tumours and they arise from blood vessels. These lesions rarely require surgical removal. Focal nodular hyperplasias (FNH) are the second most common benign tumour of the liver and they are formed as a result of congenital arteriovenous malformation due to hepatocyte response (Nichols 1989). These lesions rarely require liver surgery if they are asymptomatic. Subtypes of focal nodular hyperplasia are nodular regenerative hyperplasia and hamartomas (Nichols 1989; Sherlock 2007). These lesions are only removed if they are symptomatic or if they bleed. Hepatic adenomas (LCA) have an epithelial origin and are occasionally associated with the use of oestrogen (contraceptive pills) and steroids. They are more frequently found as solitary lesions. They carry a high risk of complications (e.g. bleeding) and require elective surgical removal. Benign lesions of the liver are usually asymptomatic. If they become symptomatic, then their symptoms usually depend on the size of the lesion. They are resected when they are symptomatic. Their common symptomatic presentations are abdominal pain, bleeding (Nichols 1989; Sherlock 2007), and occasionally, pressure symptoms (e.g. obstructive jaundice). Malignant tumours of the liver are most often secondary; the primary source of metastasis being the gastrointestinal tract (for example, colon cancer) or renal cancer, breast cancer, prostate cancer etc (Sherlock 2007).

Hepatocellular carcinoma is the most common primary liver malignancy. Other rare primary malignancies of the liver are cholangiocarcinoma, sarcoma, and
hepatoblastoma in children (Sherlock 2007).

The management of malignant tumours is discussed by multidisciplinary teams. Treatment and the decision to resect the liver are based on various factors, and the stage of malignancy is important.

Description of the intervention

Liver (hepatic) resection refers to removal of part of the liver (one or more of its vascular segments). Elective liver resection is mainly performed for benign and malignant liver tumours. In 1927, the fact that liver is not divided at the falciform ligament but that the true division occurs at the line going through the bed of the gallbladder and projects posteriorly toward the vena cava was first described (McIndoe 1927). It was later demonstrated that each true lobe was further divided into segments (Healey 1953). Couinaud (Couinaud 1957) and Goldsmith (Goldsmith 1957) extended the observations on liver anatomy, indicating that larger hepatic vein distribution was different from arterial supply and that they run between the segments and lobes rather within the lobes.

The liver is now subdivided into eight segments (I to VIII) according to the Couinaud classification (Couinaud 1957). These segments can be removed individually (segmentectomy), commonly as right hemi-hepatectomy (segments V to VIII), left hemi-hepatectomy (segments II to IV), right trisectionectomy (segments IV to VIII), or left trisectionectomy (segments II to V and VIII ± I) (Couinaud 1957; Goldsmith 1957). Resection of three or more segments is classified as major liver resection (Goldsmith 1957).

Liver resection has long been seen as a conventional 'open' operation, but the morbidity and mortality associated with this major procedure remain high (Virani 2007). With the advancement of laparoscopic skills and equipment, liver resection is selectively being carried out using this approach. Since the first laparoscopic wedge resection in the early 1990s, current work is shifting towards the feasibility of entire lobe (major) resections.

How the intervention might work

The insult to the body from laparoscopic procedures is less severe, allowing for quicker healing, fewer complications, and a shorter hospital stay (Mala 2002; Tranchart 2009). Laparoscopic surgery offers many benefits with a direct impact on patient recovery. It is potentially associated with reduced pain, quicker healing, lower wound complications, better cosmetic results, and a shorter hospital stay. It is thought to be particularly beneficial in cases where the overall aim of the procedure is not compromised and the overall safety of the procedure is maintained (Mala 2002; Belli 2007; Tranchart 2009).

Why it is important to do this review

There are still unanswered questions regarding the efficacy and safety of laparoscopic liver resection, in particular complications, long-term outcomes, completion of resection, survival advantage, and patient satisfaction. The best evidence will come from a comprehensive systemic review of randomised clinical trials. We could not identify any meta-analyses on laparoscopic versus open liver resection for benign and malignant hepatic lesions. We therefore aimed to assess laparoscopic and open liver resection for both benign and malignant lesions.

Objectives

The aim was to assess the benefits and risks associated with laparoscopic liver resection versus open liver resection for both benign and malignant hepatic lesions by conducting meta-analysis using data from available randomised clinical trials.

Methods

Criteria for considering studies for this review

Types of studies

We searched for randomised clinical trials or quasi-randomised controlled studies of patients with benign or malignant liver lesions undergoing liver resection, in which one group was treated with a laparoscopic approach and the other group with an open procedure.

Types of participants

All patients over the age of 16 undergoing laparoscopic or open liver resection for benign or malignant lesions were included. We excluded studies of participants under the age of 16 and studies based on liver resection for transplantation purposes.

Types of interventions

Laparoscopic liver resection compared with conventional open liver resection for benign and malignant lesions.

Types of outcome measures

Primary outcomes

1. All-cause mortality.
2. Quality of life.
3. Oncological clearance.
4. Adverse events (ICH-GCP 1997).

Secondary outcomes

5. Tumour resection margins.
6. Recurrence rate.
7. Number of patients requiring blood transfusion.
8. Total length of hospital stay (days).
9. Operative time (minutes).
10. Duration of stay in critical care (days).
11. Direct and indirect costs.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (Gluud 2013), Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded (Royle 2003). We also searched Clinicaltrials.gov. The search strategies with the time spans of the searches are given in Appendix 1. There was no language restriction in searching for data.

Searching other resources

We inspected all identified studies for references to more studies of interest. We cross-referenced all potential studies for the review. For unpublished and ongoing trials and duplicate publications, we planned to contact the first author of the study. We handsearched published abstracts from the following relevant conference proceedings:

  1. Association of Surgeons Great Britain and Ireland (ASGBI).

  2. Society of Academic and Research Surgery (SARS).

  3. International Hepato-Pancreato-Biliary Association (IHPBA).

  4. American Hepato-Pancreato-Biliary Association Annual Meeting (AHPBA).

  5. Asian Pacific HPA congress.

  6. Annual Meeting of the American Surgical Association.

  7. Congress of the European Hepato-Pancreato-Biliary Association (EHPBA).

  8. Great Britain and Ireland HPA Association.

Data collection and analysis

We were not able to conduct data collection and analysis because no eligible studies were identified.

Selection of studies

Two authors, IA and AR, reviewed the selected studies independently. For any disagreement about inclusion or exclusion of a study, GR reviewed the study and a consensus was reached.

Data extraction and management

We conducted the review using the standard Cochrane software Review Manager 5.2 (RevMan 2012). We were not able to identify any eligible study to
perform meta-analysis. The excluded studies are listed with the reasons for exclusion. If there was an eligible study, IA and AR would have independently conducted data extraction using a standard form.

The data on outcomes as mentioned above would have been collected from the trials, including the following information:

  1. Author, year of publication, study design, number of patients.

  2. Inclusion, exclusion and matching criteria.

  3. Mean age, conversion of laparoscopic group to open group in each study, percentage of females in each study.

  4. Risk of bias.

  5. Pathology of lesions resected, mean size of hepatic lesion, type of procedures performed.

  6. Peri-operative and postoperative parameters, early postoperative adverse outcomes, oncological clearance, long-term outcomes.

We would have sought any unclear or missing information by contacting the authors of the individual trials. The review author, GR, would have reviewed and extracted the data for the studies where there was any difference in data extraction between IA and AR. When the data become available, we will use the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) for data extraction and management.

Assessment of risk of bias in included studies

We were not able to identify any eligible trials for inclusion in this review. If eligible trials are found for future updates of the review, two authors will assess the methodology of each randomised trial independently using the criteria described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and the Cochrane Hepato-Biliary Group Module (Gluud 2013). According to empirical evidence (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savovic 2012; Savovic 2012a; Gluud 2013), we would have assessed the risk of bias of the trials based on the following bias risk domains:

Allocation sequence generation
- Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice are adequate if performed by an independent person not otherwise involved in the trial.
- Uncertain risk of bias: the method of sequence generation was not specified.
- High risk of bias: the sequence generation method was not random.

Allocation concealment
- Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomisation unit. The allocation sequence was unknown to the investigators (for example, if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).
- Uncertain risk of bias: the method used to conceal the allocation was not described so that intervention allocations may have been foreseen in advance of, or during, enrolment.
- High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants, personnel, and outcome assessors
- Low risk of bias: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.
- Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.
- High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes were likely to be influenced by lack of blinding.

Incomplete outcome data
- Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, has been employed to handle missing data.
- Uncertain risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.
- High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting
- Low risk of bias: all outcomes were pre-defined and reported, or all clinically relevant and reasonably expected outcomes were reported.
- Uncertain risk of bias: it is unclear whether all pre-defined and clinically relevant and reasonably expected outcomes were reported.
- High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported, and data on these outcomes were likely to have been recorded.

For a trial to be assessed with low risk of bias in the selective outcome reporting domain, the trial should have been registered either on the www.clinicaltrials.gov web site or a similar register, or there should be a protocol, eg, published in a paper journal. In the case when the trial was run and published in the years when trial registration was not required, we would carefully scrutinize all publications reporting on the trial to identify the trial objectives and outcomes. If usable data on all outcomes specified in the trial objectives are provided in the publications results section, then the trial can be considered low risk of bias trial in the Selective outcome reporting domain.

For-profit bias
- Low risk of bias: the trial appears to be free of industry sponsorship or other kind of for-profit support that may manipulate the trial design, conductance, or results of the trial.
- Uncertain risk of bias: the trial may or may not be free of for-profit bias as no information on clinical trial support or sponsorship is provided.
- High risk of bias: the trial is sponsored by the industry or has received other kind of for-profit support.

If the risk of bias in a trial was judged as 'low' in all the above domains, the trial was to fall in the 'low risk of bias' group of trials. Likewise, if the risk of bias was judged as 'uncertain' or 'high', then the trial was to fall in the 'high risk of bias' group of trials.

Measures of treatment effect

Treatment effect was not measured due to absence of data from randomised clinical trials. However, in future we will analyse the differences in the outcome of continuous variables between the two groups using mean difference (MD) or standardised mean difference (SMD). This will take into account the effect of sample size (DerSimonian 1986). The analysis will include only the continuous variables with corresponding standard deviations reported in the trials. If standard deviations are not stated for the individual study outcomes, we will obtain them from standard errors, confidence intervals, t values or P values that relate to the differences between the means in the two groups as stated in the trials. This will be done to standardise all the data (DerSimonian 1986). We will use risk ratios (RR) to compare categorical outcomes between the two groups (DerSimonian 1986). We will report each analysed value with its 95% confidence interval (CI). We will measure mortality as a time-to-event outcome and use the hazard ratio (HR) to compare the groups (Higgins 2011). We will contact trial authors for any missing information and clarification about the statistics.

Unit of analysis issues

In the future, we will analyse each included trial for the level at which randomisation occurred. For each trial, we will consider the following:

  1. If there are repeated observations on the participants, we will obtain individual patient data and conduct time-to-event analyses that use the whole follow-up for each participant.

  2. If the outcomes of interest are repeated more than once, we will take care to avoid unit of analysis errors and we will not treat count data as dichotomous.

Dealing with missing data

In the future, if we find data from randomised clinical trials that can be included in the review, we will contact the contact person of the trial to ask for any missing data for inclusion in the final analysis. In case of post-randomisation exclusions from the trial, we will perform available patient analysis (Higgins 2011).

Assessment of heterogeneity

In the future, when data of interest to this review are available, we will use the I2 statistic to quantify heterogeneity across trials. Its importance depends on the magnitude and direction of effects and the strength of evidence of heterogeneity (Higgins 2011). The rough estimate of I2 is indicated below (Higgins 2011):

  1. 0% to 40%: might not be important.

  2. 30% to 60%: moderate heterogeneity.

  3. 50% to 90%: substantial heterogeneity.

  4. 75% to 100%: considerable heterogeneity.

Assessment of reporting biases

When randomised trials are found, we will assess publication bias using a funnel plot which is a graphical exploration of a scatterplot of treatment effect against a measure of study size (Sterne 2001). If the funnel plot is asymmetrical, suggesting unpublished negative trials, its interpretation will be beneficial if more than five trials are included in the plot (Tang 2000).

Data synthesis

Without any included randomised clinical trials, data synthesis was not possible. Upon inclusion of future randomised trials, we will synthesise the data as follows:

  1. We will collect all the data, along with their variance, range or standard deviations. We will measure the outcomes in terms of dichotomous and continuous data.

  2. We will perform both random-effects and fixed-effect model analyses, and in case of significant discrepancies in the results, we will use one of the model results. For example, if there is increased heterogeneity between the trials, we will use the inverse-variance method and random-effects model. However, if there are a low number of events or small study sample size for any outcome, then we will use the fixed-effect Mantel-Haenszel method.

  3. We will use mean difference to summarise statistics used for meta-analysis of continuous data. If for a particular outcome the data are collected both in the form of dichotomous and continuous variables, then we will record means and standard deviations for continuous outcomes as well as for dichotomous outcomes, and we will enter all the data in text form as 'Other data' outcomes.

  4. We will combine time-to-event outcomes using the generic inverse variance method. If different scales are used for measuring quality of life, we will use the standardised mean difference.

  5. We will also perform trial sequential analysis (TSA) to prevent inflation of the risk of falsely inferring a statistically significant difference between two interventions under investigation by repeated statistical hypothesis testing (CTU 2011; Thorlund 2011). This method limits the risk of inferring that no difference exists between two interventions due to repeated statistical hypothesis when in truth there is a difference (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010). TSA is a methodology that combines an information size calculation (cumulated sample sizes of included trials) with the threshold of statistical significance. We will conduct TSA on the data from the trials with low risk of bias (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009; Thorlund 2010). It will include primary outcomes as stated earlier in the protocol.

  6. We will perform sensitivity analysis using an a priori intervention effect of 20% risk ratio reduction, a risk of type I error of 5% and a risk of type II error of 20%. For all dichotomous data, risk ratio reduction will be the unit of intervention effect. With a priori assumed final heterogeneity of 50% and heterogeneity estimation (I2), we will obtain the observed heterogeneity adjustment factor [1/(1-I2)] (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010).

  7. We will summarise the evidence in a 'Summary of findings' table using GRADEpro (http://ims.cochrane.org/revman/other-resources/gradepro).

Subgroup analysis and investigation of heterogeneity

We would have performed subgroup analysis on trials comparing laparoscopic and open procedure groups for: different types of lesions (benign and malignant), types of liver resection (left lateral, wedge and right hepatectomy), and level of risk of bias (low and high-risk trials). We would have used the Chi2 test for differences between subgroups.

Sensitivity analysis

In the analysis of future included trials, when available, we will perform sensitivity analysis for any numerical values, review criteria, or trial outcomes that are arbitrary, to exclude any dependence of the results of meta-analysis on unclear or arbitrary decisions. The first analysis will include all trials and the repeat analysis (that is, the sensitivity analysis) will exclude any trials or methodology that contain unclear decisions.

Results

Description of studies

Characteristics of the ongoing studies and excluded studies are provided in the review tables (Characteristics of ongoing studies; Characteristics of excluded studies).

Risk of bias in included studies

No suitable trials were identified for inclusion.

Effects of interventions

Effects of interventions are not reported as no trials are included currently.

Discussion

Hepatectomy is currently performed mainly by means of two techniques: open and laparoscopic. The safety and feasibility data available for both techniques have been established by previous case series and observational studies. The first open liver resection (OLR) was reported by Ichio Honjo (Kyoto University) in 1949 (Tsuchiya 1989). The procedure of liver resection became widespread across different global centres after the vascular anatomy of the liver was established, by which the liver was divided into segments with independent blood supply. Over the last few years, the evolution of hepatectomy has led to a focus on a minimally invasive liver resection technique (Topal 2008), resulting in the first laparoscopic liver resection (LLR), as reported by Gagner et al in 1992 (Gagner 2004; Topal 2008).

In the 1990s, the effectiveness and safety of the laparoscopic approach for liver resection improved due to surgeons gaining more experience and new technological instruments (Simillis 2007). Hand-assisted laparoscopy was also commonly used for better access to liver lesions. Recent NICE guidelines recommend the use of laparoscopic resection for solitary liver metastasis from colorectal cancer and, where possible, its use in the treatment of hepatocellular carcinoma (HCC) and for benign liver tumours or cysts (NICE 2005). LLR is now used for the management of both benign and malignant liver tumours (Topal 2008). It is commonly performed for peripheral tumours, in particular left lateral sectionectomy (Topal 2008). 

A previous systematic review was conducted of more than 25 observational studies of liver resection (Rao 2012). The data from these observational studies were extracted and compiled to look at different peri-operative and postoperative outcomes. It included comparative analysis and studies that compared laparoscopic and open liver resection for both benign and malignant lesions. The laparoscopic group showed lower significant overall complication rates compared to the open procedure group. Since this analysis was conducted on observational studies, it has certain inherent limitations. Each study was biased towards the laparoscopic approach. Patient selection, type of liver resection, and selected matching of the patients in each study limited the generalisability of the results (Rao 2012). The results of the studies included in the review depended on the experience of the laparoscopic surgeons in that centre. Hence, there was significant heterogeneity between the studies in the peri-operative outcome measurements (Rao 2011a).  

Laparoscopic left lateral sectionectomy rapidly gained the interest of hepatobiliary surgeons due to the easy accessibility of the left lateral segment (Soubrane 2006; Aldrighetti 2008; Rao 2011a). Hence, it has become one of the commonest types of laparoscopic hepatic resection to be carried out. There have been observational studies reporting the increased efficiency and safety of the laparoscopic left lateral sectionectomy (Soubrane 2006). Some studies have directly compared laparoscopic to open left lateral sectionectomy (Tang 2005; Aldrighetti 2008). However, there is still no randomised clinical trial or meta-analysis comparing these two kinds of hepatic resection.

A similar review was conducted comparing the laparoscopic and open approach towards left lateral liver resection only (Rao 2011a). It was based on data compilation from seven observational studies. The laparoscopic group had a lower overall complication rate compared to the open group. The authors described an urgent need for randomised clinical trials to elucidate the efficacy and safety of left lateral laparoscopic liver resection over the open approach (Rao 2011a).

In recent years, laparoscopic liver resection surgery has increasingly been carried out for malignant lesions (Sarpel 2009; Tranchart 2009). However, evidence from comparisons between laparoscopic versus open hepatic resection of malignant tumours is still scarce. Some observational studies have directly compared the peri- and postoperative outcomes of laparoscopic and open liver resection for hepatic malignant lesions (Mala 2002; Sarpel 2009; Tranchart 2009), and some have evaluated outcomes such as long-term survival up to three and five years (Mala 2002; Tranchart 2009).

A systemic review has compared laparoscopic and open liver resection for malignant lesions only (Rao 2011). The data were based on previous observational studies only. The data showed that the laparoscopic group had a lower number of patients requiring blood transfusion and reduced positive resection margins. Similarly, the laparoscopic group had a lower overall complication rate than the open group. The review included 10 observational studies with 700 patients in total (Rao 2011). Most studies had laparoscopic and open groups that were matched for demographics and patient characteristics. It included patients with cirrhosis and moderate to severe co-morbidity (ASA grade II and above) to take into account common factors associated with the resection of malignant lesions (Rao 2011). Surgeons are hesitant to use the laparoscopic approach for resection of malignant liver lesions because of the limited access (Belli 2007; Castaing 2009) and fear of incomplete resection. However, the data compilation based on observational studies was in favour of the laparoscopic technique, with reduced positive resection margins as compared to open liver resection (Rao 2011). However, there was no difference in recurrence or five and three-year survival rates between the two groups (Rao 2011).

Hence, all the previous evidence regarding the efficacy of the laparoscopic approach in the resection of liver lesions is based on prospective and retrospective cohort studies. Some of these studies were conducted 20 years ago (Simillis 2007). The majority of these studies were single-centred (Rao 2012). The skill needed for the laparoscopic approach requires rigorous training. The results of these studies are also based on the training grade of the laparoscopic surgeon, the number of procedures performed in each unit, and surgical preferences (Cai 2008; Dagher 2009; Endo 2009). Inherently, there is bias associated with previous observational studies; it would be difficult to draw conclusions about any of the outcomes defined in this review on the basis of a systemic review of observational studies comparing laparoscopic and open liver resection (Rao 2011a).

Previous comparative studies, with both retrospective and prospective data collection, have mainly been conducted over the last 20 years. Most studies have matched laparoscopic and open groups to reduce bias and any confounding factors (Simillis 2007; Rao 2012). They have mentioned the type of lesions, indication for surgery, and type of hepatic resection clearly. The results for most peri-operative and postoperative outcomes in previous reviews are in favour of the laparoscopic group but with significant heterogeneity between studies (Rao 2011; Rao 2012). The most common liver resections noted in previous reviews were the wedge resection and left lateral hepatic resection (Rao 2011a; Rao 2012). These operations are assumed to be easier to conduct due to the easy access for the resection and the relative safety compared to other anatomic liver resections. No previous reviews with comparative analysis have been able to provide conclusive evidence of the better efficacy and safety of laparoscopic liver resection over the open approach because most of the results are associated with significant heterogeneity (Simillis 2007; Rao 2011; Rao 2011a; Rao 2012). All have emphasised the need for randomised clinical trials for better comparative analysis of the two techniques (Rao 2011; Rao 2012).

No current randomised clinical trial has compared the two approaches for liver resection; however, future studies are promising to provide high-level evidence on the topic. As mentioned in this review, two double-blinded, prospective, randomised clinical trials are ongoing (NCT00874224; NCT01441856). Both trials compare two groups: laparoscopic and open liver resection. Both trials are multi-centred and are headed by same research group. It will be interesting to see the published data from these trials, which will help us review the clinical management of patients with liver lesions requiring resection.

Authors' conclusions

Implications for practice

Due to the lack of available evidence, no conclusions can be drawn on the benefits and harm of the use of laparoscopic liver resection versus an open approach. The clinical judgement of experts in the field should dictate local health policy on which approach to consider for the resection of liver lesions.

Implications for research

An urgent need for randomised clinical trials exists; these trials should report their outcomes in a standardised manner for accurate data extraction and the conduct of meta-analysis.

Acknowledgements

Data reviewer: Ghaus Rao, UK (in case of discrepancy in the data extraction and review between the two authors).
Managing Editor (The Cochrane Hepato-Biliary Group): Dimitranka Nikolova, Denmark.

Peer Reviewer: Bassam Alkari, UK.
Contact Editor: Kurinchi Selvan Gurusamy, UK.

Data and analyses

Download statistical data

This review has no analyses.

Appendices

Appendix 1. Search strategies

DatabaseTime spanSearch strategy
Cochrane Hepato-Biliary Group Controlled Trials RegisterFebruary 2013(laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*) AND (((liver OR hepatic) AND (resection* OR segmentectom*)) OR hepatectom*))
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane LibraryFebruary 2013#1 MeSH descriptor Laparoscopy explode all trees
#2 laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*
#3 (#1 OR #2)
#4 MeSH descriptor Hepatectomy explode all trees
#5 ((liver OR hepatic) AND (resection* OR segmentectom*)) OR hepatectom*
#6 (#4 OR #5)
#7 (#3 AND #6)
MEDLINE (Ovid SP)1946 to February 20131. exp Laparoscopy/
2. (laparoscop* or coelioscop* or celioscop* or peritoneoscop*).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]
3. 1 or 2
4. exp Hepatectomy/
5. (((liver or hepatic) and (resection* or segmentectom*)) or hepatectom*).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]
6. 4 or 5
7. 3 and 6
8. (random* or blind* or placebo* or meta-analysis).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]
9. 7 and 8
EMBASE (Ovid SP)1974 to February 20131. exp laparoscopy/
2. (laparoscop* or coelioscop* or celioscop* or peritoneoscop*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
3. 1 or 2
4. exp liver resection/
5. (((liver or hepatic) and (resection* or segmentectom*)) or hepatectom*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
6. 4 or 5
7. 3 and 6
8. (random* or blind* or placebo* or meta-analysis).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
9. 7 and 8
Science Citation Index Expanded (http://apps.webofknowledge.com)1900 to February 2013# 1 TS=(laparoscop* or coelioscop* or celioscop* or peritoneoscop*)
# 2 TS=(((liver or hepatic) and (resection* or segmentectom*)) or hepatectom*)
# 3 #2 AND #1
# 4 TS=(random* or blind* or placebo* or meta-analysis)
# 5 #4 AND #3
Clinicaltrials.govFebruary 2013(laparoscopy) AND (((liver OR hepatic) AND (resection* OR segmentectom*)) OR hepatectom*))

Contributions of authors

Irfan Ahmed: initiated the review, wrote the protocol and review.
Rao Ahsan: wrote the protocol and the review.
Both authors agreed on the final version.

Declarations of interest

Irfan Ahmed is the consultant laparoscopic and hepato-pancreato-biliary surgeon at Aberdeen Royal Infirmary. Ahsan Rao is a core surgical trainee for East of Scotland deanery. Both have been authors of the systematic reviews comparing laparoscopic and open liver resection conducted on previous non-randomised comparative studies.

Sources of support

Internal sources

  • Aberdeen Royal Infirmary and University of Aberdeen, UK.

External sources

  • No sources of support supplied

Differences between protocol and review

There are no differences between protocol and review.

Characteristics of studies

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Abu Hilal 2008Non-randomised, comparative analysis with prospective laparoscopic group matched with retrospective open group
Aldrighetti 2008Retrospective, non-randomised comparative analysis
Belli 2007Retrospective, non-randomised comparative analysis
Belli 2009Retrospective, non-randomised comparative analysis
Buell 2004Comparative case series of prospective laparoscopic group
Cai 2008Retrospective, non-randomised comparative analysis
Campos 2009Non-randomised, prospective, observational study (laparoscopic group matched with retrospective open group)
Carswell 2009Retrospective, non-randomised, comparative analysis
Castaing 2009Retrospective, non-randomised, comparative analysis
Dagher 2009Retrospective, non-randomised, comparative analysis
Endo 2009Retrospective, non-randomised, comparative analysis
Farges 2002Non-randomised, comparative cohort study
Ito 2009Retrospective, non-randomised comparative analysis
Kaneko 2005Non-randomised, comparative cohort study
Koffron 2007Retrospective, non-randomised comparative analysis
Laurent 2003Non-randomised, comparative cohort study
Lee 2007Case-control study
Lesurtel 2003Case-control study
Mala 2002Non-randomised, retrospective, comparative study
Mamada 2007Retrospective, non-randomised, comparative analysis
Morino 2003Retrospective, non-randomised, comparative analysis
Polignano 2008Non-randomised, prospective cohort study
Rau 1998Non-randomised, prospective cohort study
Rowe 2009Non-randomised, prospective cohort study
Sarpel 2009Retrospective, matched cohort study
Soubrane 2006Non-randomised comparative study (prospective laparoscopic group matched with retrospective open group)
Tang 2005Retrospective, matched comparative study
Topal 2008Non-randomised, prospective comparative study
Tranchart 2009Non-randomised comparative study
Troisi 2008Retrospective, non-randomised comparative analysis
Tsinberg 2009Case-control study
Vanounou 2010Retrospective, matched cohort study

Characteristics of ongoing studies [ordered by study ID]

NCT00874224

Trial name or titleOpen versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERASW programme (ORANGE II – Trial): study protocol for a randomised controlled trial.
MethodsThe ORANGE-II trial is a multi-centred, prospective, randomised, controlled, parallel-group superiority trial with a double-blinded experimental and a prospective registry design to determine whether laparoscopic surgery is to be preferred over open surgery in patients undergoing a left lateral hepatic sectionectomy within an enhanced recovery programme. The experimental design produces 2 randomised arms: (a) open LLS and (b) laparoscopic LLS. Two additional registry arms will be based on surgeons/patients that do not want to be randomised because they have an explicit preference for either the laparoscopic LLS (c), or for the open LLS (d).
Participants

Inclusion criteria:

  • Patients suitable for undergoing both laparoscopic left lateral sectionectomy as well as open left lateral sectionectomy of the liver

  • Able to understand the nature of the study and what will be required of them

  • Men and non-pregnant, non-lactating women between age 18 and 80

  • BMI between 18 and 35

  • Patients with ASA I-II-III.

Exclusion criteria:

  • Inability to give written informed consent

  • Patients undergoing liver resection other than left lateral hepatic sectionectomy

  • Patients with ASA IV-V

  • Underlying liver disease.

Interventions

The experimental design produces 2 randomised arms:

Procedure: laparoscopic left lateral hepatic sectionectomy.
Procedure: open left lateral hepatic sectionectomy.

Outcomes

The primary outcome of the ORANGE II trial is time to functional recovery. The functional recovery criteria consist of adequate pain control with oral analgesics only, mobility restored to an independent level, absence of intravenous fluid administration, ability to eat solid foods and finally a normal or decreasing serum bilirubin level. A patient is fully functionally recovered when all of the 5 criteria are satisfied.

Secondary outcomes of this trial are postoperative length of hospital stay, readmission percentage, (liver-specific) morbidity, quality of life, body image and cosmetic result, hospital and societal costs during 1 year and long-term incidence of incisional hernias.

Starting dateJanuary 2010
Contact informationContact: Ronald M van Dam, MD
Phone: +31 433876543
r.vandam@mumc.nl
Notes 

NCT01441856

  1. a

    BMI: body mass index

Trial name or titleThe ORANGE II PLUS - Trial: Open versus laparoscopic hemihepatectomy.
MethodsThe ORANGE II PLUS - trial is a prospective study with a 2-armed, randomised, double-blinded experimental design and registry to determine whether laparoscopic surgery is to be preferred over open surgery in patients undergoing a left or right hemihepatectomy and participating in an enhanced recovery programme.
Participants

Inclusion criteria:

  • Patients requiring open or laparoscopic left/right hemihepatectomy

  • Able to understand the nature of the study and what will be required of them

  • Men and non-pregnant, non-lactating women between age 18 and 80

  • BMI between 18 and 35

  • Patients with ASA I-II-III.

Exclusion criteria:

  • Inability to give written informed consent

  • Patients undergoing liver resection other than left or right hemihepatectomy

  • Patients with hepatic lesion(s), that are located with insufficient margin from vascular or biliary structures to be operated laparoscopically

  • Patients with ASA IV-V

  • Underlying liver disease: significant fibrosis (METAVIR score F2-F4), indirect signs of CASH (platelet count < 100,000, splenomegaly, severe steatosis)

  • Repeat hepatectomy.

Not willing to participate.

InterventionsTwo groups (left and right) will receive an open hemihepatectomy, and the other 2 groups (left and right) will receive a laparoscopic hemihepatectomy. Patients ineligible for randomisation will be included in a prospective registry. All patients will participate in an enhanced recovery programme.
Outcomes

Primary outcomes: time to functional recovery.

Secondary outcomes: length of hospital stay, total percentage of patients being readmitted total morbidity during 1 year, composite endpoint of liver-specific morbidity (intra-abdominal bleeding, intra-abdominal abscess, ascites, post-resectional liver failure, intra-operative mortality, bile leakage), long-term incidence of incisional hernia, quality of life, body image and cosmesis, and reasons for delay in discharge after functional recovery.

Starting dateJanuary 2012
Contact informationRonald M. van Dam, MD
Telephone: +31 43 387 74 89
r.vandam@mumc.nl
Notes 

Ancillary