International Study on the Outcomes of Liver Surgery - LiverGroup.Org
Conditions: Liver Diseases
Sponsor: Royal Free Hospital NHS Foundation Trust

 
 
 
1 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
 
International Snapshot Study on the Outcomes of Liver surgery - 
LiverGroup.org 
 
The LiverGroup.org Collaborative1,2,3  
 
Affiliations/Sponsors 
1. Department of HPB Surgery and Liver Transplantation, Royal Free Hospital NHS 
Foundation Trust, UCL Partners, London, UK 
2. Department of Surgery, University Hospital Miguel Servet, University of Zaragoza, Spain 
3. All affiliations of the LiverGroup.org Team Members 
 
Trial registration: Awaiting submission at ClinicalTrials.gov 
 
Protocol version: v1.3, 30 November 2018 (written by Erik Schadde, Dimitri Aristotle Raptis and 
Thomas Hanna), approved by the Chief Investigators and all Members of the Steering Committee, 
see below).  
 
Funding: The sponsors are the Royal Free Hospital in London, UK and the University of Zaragoza 
in Spain. There are no industry funders allocated to this study.  
 
Roles and responsibilities: The headquarters acting as the coordinating centre is located at the 
Royal Free Hospital in London, UK run by Dr. Dimitri Aristotle Raptis, Prof. Massimo Malagò and 
the Management Committee. The Chief Investigators of LiverGroup.org are Prof. Alejandro 
Serrablo from the University of Zaragoza, Spain and Prof. Massimo Malagò from the Royal Free 
Hospital, London, UK. The complete list of the LiverGroup.org Team is available at: 
https://livergroup.org/?q=team. The responsibilities of the members of the Management 
Committee are, among others facilitating the group’s decision-making processes, distributing 
newsletters, announcements and invitation letters, safeguarding and applying regulations, 
arranging regular committee and general meetings of the group, recording decisions and tasks 
clearly, and providing support to the collaborators. The Steering Committee Members are: Christos 
Dervenis (Greece), Karl Jürgen Oldhafer (Germany), Marcel Autran Machado (Brazil), Martin Hertl 
(Chicago), Norihiro Kokudo (Japan), Pål-Dag Line (Norway) Roberto Hernandez-Alejandro 
(Canada), Stefan Breiteinstein (Switzerland), Thomas van Gulik (Netherlands), Yaman Tokat 
(Turkey) and (Ulf Peter Neumann (Germany). Their responsibilities include, among others 
overseeing and controlling the scientific part of the project and giving strategic direction and 
support to the members of the management committee. The Members of the Steering Committee 
have approved the study design and protocol of the LiverGroup.org Study. The Country Leaders 
are responsible for recruiting centers within their country/region. Additionally, Auditors (data 
monitors) will be assigned to monitor the adherence to the protocol as well as auditing the quality 
of data collection of the different participating centers.  

 
 
 
2 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
Summary 
 
Introduction:  Liver surgery was associated with at least 10% mortality in the 1970’s. The safety of 
liver surgery has dramatically improved since with a mortality now of around 1-2%. Individual centres 
put the bar even higher and postulate that a perioperative mortality close to 0% should be the 
standard of major liver resection. Despite these claims, epidemiological studies paint a different 
picture again with a mortality rate of 6%. 
 
Eligibility: Any surgeon performing liver resections is eligible to participate in LiverGroup.org. All 
consecutive cases must be included and there are no minimum patient numbers per centre. Liver 
transplantation is excluded. 
 
Time period and team members: Each participant may form a team of 3 members in total. There will 
be 3 months of prospective patient enrolment and 3 months follow up within a 12-month frame (Jan – 
Dec 2019).  
 
Inclusion criteria: All liver resections will be included: 
• 
All indications (including benign and living donor resections), all co-morbidities 
• 
Open, laparoscopic or robotic 
• 
Single wedge resections to extended liver resections 
• 
Single or two-stage hepatectomies 
• 
Procedures with liver volume enhancement such as PVE, PVL, ALPPS.  
• 
Resections involving cold perfusion (ex-situ and ante-situ) 
• 
There are no exclusion criteria as related to indication, age or comorbidities.  
 
Exclusion criteria: 
• 
Liver transplantation 
• 
CT-guided RFA, MWA, etc. 
• 
Liver biopsies 
 
Audit Standard: An audit of the consecutivity, intent-to-treat and completeness of data entered will 
be performed by random selection of at least 30% of the contributing surgeons. A member of 
LiverGroup.org will be assigned to audit one fellow surgeon of LiverGroup.org to perform a validation 
of the number of deaths and of the death dates.  
 
Outcomes: the primary endpoint of the analysis will be 90-day mortality. Secondary endpoints will be 
liver failure, complications, and length of stay and incidence of re-hospitalisation. 
 
Data ownership: The study sponsors, the Royal Free Hospital London and University of Zaragoza, 
will act as the custodians of the data. The steering and management committees together will decide 
after the publication of the main report about requests regarding secondary analysis and will consider 
all such requests based on quality and the validity of the proposed project and decide by majority 
decision. 
 
Authorship: A single analysis and reporting without hierarchical authorship (no first author, no last 
author) is planned at the end of the study (a “pure” group author publication) to reflect the 
collaborative effort.  
 
Register: Please register your interest for participation at:  
https://LiverGroup.org/?q=register  
 

 
 
 
3 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
Introduction 
The safety of major liver surgery, defined as resection of four or more hepatic segments has 
improved significantly in recent decades with mortality rates improving from 10% in the 1970’s1 
to 1-2% currently.2-5  Some individual centres are now reporting perioperative mortality rates 
approaching 0%,4,6 yet epidemiological studies suggest much higher mortality rates of up to 
6%;7 the reasons for this discrepancy are not completely understood. 
 
Complexity and extent of liver surgery, patient selection and both centre and surgeon 
experience are all cited factors which may influence outcomes following major liver surgery. A 
large, single-centre analysis of outcomes following liver surgery found that the number of 
hepatic segments resected and operative blood loss were the only two predictors of both 
perioperative morbidity and mortality.5 The authors suggest that whilst ‘complex liver 
resections’ defined as liver surgery with one or more major extrahepatic procedure, were 
associated with a higher mortality in conjunction with major hepatectomies, complexity had no 
impact on mortality when performed with minor hepatectomies, thus highlighting the 
importance of future liver remnant percentage (FLR) which has since been repeatedly 
demonstrated.8,9 Induction of regeneration prior to resection using portal vein embolization, 
portal vein ligation or Associating Liver Partition and Portal vein ligation for Staged 
hepatectomy (ALPPS) are evolving strategies to mitigate the adverse outcomes associated 
with a major liver surgery. Such staged approaches to major liver resections are associated 
with a perioperative mortality of over 5% even in the most experienced centers12-14 with the 
ALPPS procedure reported to have a mortality of 12% in voluntary registry studies.15 Whether 
such strategies improve the safety of major liver surgery, or instead allow a more aggressive 
approach to resection of lesions previously deemed unresectable is contentious. 
 
At the extreme end of complexity are ex-situ and ante-situ resections. The largest series of 
standardized in-situ hypothermic perfusion for patients with tumours involving the 
vena cava and the hepato-caval junction identified an overall mortality rate of 20%.18   
 
An open debate and ultimately consensus amongst the HPB surgical community is required 
to address the delicate balance between improving mortality of liver surgery whilst developing 
approaches to treat the most challenging lesions. To inform this debate a robust prospective 
audit examining the current international experience and outcomes is required. Existing 
registry studies are  based on national (French Liver surgery registry, Scandinavian liver 
surgery registry LiverMET Survey SweLiv21, Italian laparoscopic liver surgery registry22) or 

 
 
 
4 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
international collaborations (e.g. the ALPPS registry initiated in 2012, www.ALPPS.net15) are 
commendable attempts to provide valid data.  They have however either not been international 
in scope, proprietary in character or have underestimated the true incidence of morbidity and 
mortality due to voluntary and selective reporting of patients or lack of monitoring of data entry. 
Large single centre studies both in Europe and the US with high quality retrospective 
databases have provided the most robust data,3,5,6 but across a long enrolment periods and 
with a considerable era and centre bias. Furthermore, series from high volume, single centre, 
specialised units represents only the ‘tip of the iceberg’ of practice of liver resection worldwide.  
 
The International Liver Surgery Outcomes Study – LiverGroup.org aims to measure the true 
worldwide practice of Liver surgery and associated outcomes by recruiting multiple 
international centres, committing to consecutive patient registration per surgeon and undergo 
rigorous data validation. It is hoped that these data will provide a more appropriate guide to 
inform surgeons and patients to assess which level of complexity should be routinely offered 
for high tumour burden and anatomically difficult scenarios. 
 
Methods 
Participants, interventions and outcomes 
Study setting 
This will be an International Liver Surgery Outcomes Study where all centres performing liver 
surgery world-wide will be able to participate. The current preliminary list of study sites is 
available at https://livergroup.org/?q=team.  
 
Eligibility criteria 
All patients undergoing liver resection by single surgeons at their respective centres are 
eligible for study inclusion. The inclusion criteria are patients 18 years of age or older, any 
indication for surgery, including benign and living donor resections, open, laparoscopic, hybrid 
or robotic approaches. Furthermore, any extent of liver resection is included, from single 
wedge resections to extended liver resections. Procedures with liver volume enhancement 
such as PVE, PVL, ALPPS, resections involving cold perfusion (ex-situ and ante-situ) are also 
included. The exclusion criteria are patients undergoing liver transplantation, liver biopsies or 
image-guided liver ablation alone.  
 
 
 

 
 
 
5 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
Outcomes 
 
The primary objectives of LiverGroup.org is to develop a non-proprietary international data set 
on the morbidity and mortality following liver resections among international surgeons. 
Morbidity will be recorded according to the Clavien-Dindo Classification of Surgical 
Complications, the FABIB Liver Surgery-Specific Classification and the novel Comprehensive 
Complication Index® (CCI®). Mortality will be captured until the 90th postoperative day.  
 
The secondary objective is to identify independent risk factors for morbidity and mortality using 
multivariable regression models. 
 
Participant timeline and study duration 
The enrolment period will last 3 months and a minimum of 3 months period is required for follow-
up of each patient. Surgeons may start enrolment at any time within the 12-month enrolment time 
frame: 1st of January 2019 until the 31st of December 2019. The Management Committee may 
decide to prolong the patient enrolment if deemed necessary. 
 
Sample size 
The study aims for the maximum number of patients it will be able to recruit and has no power 
calculation for specific outcomes. Assuming a 2.5% 90-day mortality rate, at least 2000 patients 
will have to be recruited to be able to perform a meaningful multivariate analysis on independent 
risk factors postoperative mortality 
 
Recruitment 
Surgeons joining LiverGroup.org are encouraged to propose a country or regional leader 
(north/south etc). This process will be guided by the management committee. The responsibilities 
of the Regional and Country Leaders representing each country in the world include, among others 
to recruit and co-ordinate collaborators in their own country or region as well as to provide 
additional scientific and administrative support to their collaborators. Additionally, personal 
contacts of the LiverGroup.org team will be used to recruit centres. Furthermore, the members of 
the Management Committee are seeking for endorsement of the International Hepato-Pancreato-
Biliary Association (IHPBA), European-African Hepato-Pancreato-Biliary Association (E-AHPBA), 
the American Hepato-Pancreato-Biliary Association (AHPBA), and the Asian-Pacific Hepato-
Pancreato-Biliary Association (A-PHPBA).  
 

 
 
 
6 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
Data collection, management, and analysis 
Study data 
Data are “surgeon-based”, not “centre-based”. Surgeons participating in LiverGroup.org are only 
responsible for their own data. The data will indicate in an anoymized fashion that surgeons belong 
to a specific centre. Data will be entered using a personalized login assigned to surgeons, their 
assistants and in some centres, study nurses. The complete dataset of the electronic Case Report 
Form (CRF) are available at https://livergroup.org/?q=instructions.  
 
Each CRF has a unique identifier. A participant may enter data for a colleague or partner under 
their login, as long as authorization has been granted by the user. If centres are not willing to 
disclose their identity to the management committee when asked to do so for the purpose of an 
audit, they are free to have their data excluded from the analysis. Such exclusion will be reported 
in the final report for transparency while assuring that the data are under control of the individual 
centre until the final analysis and audit is performed.  
 
Data collection 
Data will be entered directly onto the electronic CRF available at https://livergroup.org/?q=CRF 
which includes the unique identifier. Collaborators keep a paper key list connecting the unique 
database identifier with the patient name in a safe place locked away under their control and their 
responsibility. If the list gets lost and audit is impossible, the surgeons’ data will be excluded from 
the final analysis and reported in the final report. The LiverGroup.org management committee 
cannot identify an individual patient or surgeon or centre without contacting the local PI who 
entered the data and is in possession of the key to the data.  
 
Data collection methods 
 
The Management Committee currently consists of clinicians who will review data entered, monitor 
progress and maintain the platform and send reminders to the participants regarding completion 
of data or questions regarding clarifications. Any collaborator is welcome to join the Management 
Committee. This practice is introduced to avoid the proprietary use of the collected data by a few 
“founding members” or “coordinators” or members of an appointed “scientific committee”. 
 
To avoid selective reporting, all consecutive patients undergoing liver resections by one individual 
surgeon over three months are included. In some patients the operation may not run the expected 
course, be aborted or changed in scope. Intraoperative findings may change the operative plan. 
These patients should also be recorded in the registry following the principle of intent-to treat to 
avoid incomplete reporting. 
 

 
 
 
7 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
An audit of the consecutively, intent-to-treat, completeness of data entered will be performed by 
random selection of the contributing surgeons. A member of LiverGroup.org will be assigned to 
audit one fellow surgeon of LiverGroup.org to perform a validation of the number of and date of 
deaths. This randomly assigned peer-review by participating centres is entirely novel and has not 
been routinely performed in similar snapshot studies, to the best of our knowledge. In detail, e.g. 
a surgeon/monitor from site A will monitor site B while a surgeon/monitor from site B will monitor 
site C. The monitors themselves may want to carry the costs for the monitoring, but in case that is 
not possible, LiverGroup.org may help to provide funding from third parties. 
 
As for the quality of the data collected, the electronic CRF is specially designed to force data entry 
for the important variables (e.g. comorbidities, procedure type, morbidity, mortality, etc.), has 
minimum and maximum allowed values to avoid typing errors for continuous variables, all 
categorical data are captured in the form of selection lists and there is a description for important 
variables within the CRF. Additionally, there are calculators available at LiverGroup.org (e.g. sFLR 
and conversion of lab values) to ensure uniform data capture. Furthermore, information regarding 
the Brisbane, Clavien-Dindo, FABIB, BCLC Staging, and Bismuth-Corlette classifications is also 
available at LiverGroup.org.  
 
All participants will have the opportunity to read study documents available at LiverGroup.org 
including instructions as well as contact the Management Committee in case they have questions 
directly through the platform.  
 
Data management 
LiverGroup.org is a Clinical Trial Management System (CTMS) built on Drupal 7 that will act as the 
backbone of our study, by supporting administration, collaboration, communication and information 
sharing needs among members from several centres worldwide. Anonymised patient data will be 
stored in two separate secured sites with access given only to the relevant users. There will be 
regular backups. Furthermore, the CTMS is secured with a Hypertext Transfer Protocol Secure 
(HTTPS) in combination with a SSL/TLS protocol and an encrypted SQL database.24  
 
The study sponsors, Royal Free Hospital London and University of Zaragoza, will act as the 
custodians of the data. The steering and management committees together will decide after the 
publication of the main report about requests regarding secondary analysis and will consider all 
such requests based on quality and the validity of the proposed project and decide by majority 
decision. 
 
Statistical methods 

 
 
 
8 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
The primary endpoint of the analysis will be the 90-day mortality; secondary endpoints will be liver 
failure by Clavien-Dindo score,23 the FABIB classification, complications, length of stay and 
incidence of re-hospitalisation. Descriptive statistics will be performed. Continuous variables will 
be compared with the Student t test, the Mann-Whitney U test and the Kruskal-Wallis H test or 
one-way ANOVA as appropriate. Differences among proportions derived from categorical data will 
be compared using the Fisher test and the Pearson chi-square. Univariate analysis will be 
performed to test factors associated with post-operative complications and 90-day mortality. 
Multivariable regression models will be used to identify factors independently associated with these 
outcomes and to adjust for differences in confounders. Results of the multivariable analyses will 
be reported as adjusted odds ratios (OR) with 95% confidence intervals. ROC curves and the 
Youden's index will be used to identify ideal cut-off points for continuous variables. All p values will 
be 2-sided and considered statistically significant if p<0.05. The statistical analysis will be 
performed using R version 3.3.2 (R Core Team, GNU GPL v2 License), R Studio version 1.0.44 
(RStudio, Inc. GNU Affero General Public License v3, Boston, MA, 2016) with the graphical user 
interface (GUI) rBiostatistics.com (rBiostatistics.com, London, UK, 2017). 
 
Monitoring 
The management committee will monitor the export database of all CRFs weekly. At least 30% of 
centre should have undergone on-site peer – monitoring as explained above prior to final analysis.  
 
Safety 
This trial involves no risk of bodily harm to patients or investigators. Therefore, adverse events will 
not 
be 
monitored 
or 
reported. 
Data 
confidentiality 
will 
be 
protected 
through 
local anonymization. Anonymization will be monitored and breaches of confidentiality reported. 
Individual participants are responsible toward their local authorities for breaches in confidentiality. 
 
Ethics and dissemination 
Research ethics approval 
LiverGroup.org was recognised as an audit in the UK and does not require any ethics approval. 
The principal investigator in the UK must ensure the recording of data is carried out in accordance 
with the Research Governance Framework for Health and Social Care; Second Edition, 2005, and 
its subsequent amendments. The principle investigators in the respective countries must clarify the 
need for ethics and other regulatory approvals and ensure these are in place prior to data 
collection. The management committee will collect documentation of the necessary ethics and 
other regulatory approvals from the respective centres prior to providing electronic access to 
the CRF. Since this study is effectively a large-scale international clinical audit of anonymized data 
already recorded in the course of routine patients care, we expect that in most countries no 

 
 
 
9 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
individual patient consent will be required (see above). For countries where individual consent is 
required, we will provide an informed consent form in English that may be adjusted to local 
requirements. Any not enrolled patient due to no patient consent will have to be recorded and 
reported in the final report. The English version of the patient information and consent form is 
available at https://livergroup.org/?q=instructions.  
 
LiverGroup.org will support all surgeons with their respective institutional review boards/ethics 
committee applications. Individual modifications to the generic protocol may become necessary. 
 
Declaration of interests 
The are no financial and other competing interests of the principal investigators for the overall trial 
and each study site.  
 
Access to data and dissemination policy  
LiverGroup.org is a collaboration of all surgeons contributing data as equal partners. Each 
surgeon contributing data has access to analysis files of the entire database at any time point and 
the right to propose analyses and publish data as long as every surgeon contributing data are 
included as a group author in every publication and have an opportunity to review the data prior to 
submission. Each collaborator has access to their own data in a form of excel export file without 
requiring permission or approval by the LiverGroup.org management committee.  
 
One single analysis without hierarchical authorship (no first author, no last author) is planned at 
the end of the study (a “pure” group author publication) to reflect the collaborative effort. Any 
member of the group is encouraged to step forward with secondary analyses on specific questions 
and will have full access to the data. There will be no need for approval of publication of data from 
The LiverGroup.org collaboration, but all group authors have the right to review the manuscripts 
and have to be given at least 1 week to be able to review the manuscripts. 

 
 
 
10 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
References 
1. Fortner JG, Kim DK, Maclean BJ, et al. Major hepatic resection for neoplasia: personal 
experience in 108 patients. Ann Surg 1978; 188:363-371. 
2. Fortner JG, Blumgart LH. A historic perspective of liver surgery for tumors at the end of the 
millennium. J Am Coll Surg 2001; 193:210-222. 
3. Belghiti J, Hiramatsu K, Benoist S, et al. Seven hundred forty-seven hepatectomies in 
the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000; 
191:38-46. 
4. Fan ST, Lo CM, Liu CL, et al. Hepatectomy for hepatocellular carcinoma: toward zero 
hospital deaths. Ann Surg 1999; 229:322-330. 
5. Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic 
resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002; 
236:397-406; discussion 406-397. 
6. Imamura H, Seyama Y, Kokudo N, et al. One thousand fifty-six hepatectomies without 
mortality in 8 years. Arch Surg 2003; 138:1198-1206; discussion 1206. 
7. Asiyanbola B, Chang D, Gleisner AL, et al. Operative mortality after hepatic resection: are 
literature-based rates broadly applicable? J Gastrointest Surg 2008; 12:842-851. 
8. Kishi Y, Abdalla EK, Chun YS, et al. Three hundred and one consecutive extended 
right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg 
2009; 250:540-548. 
9. Lang H, Sotiropoulos GC, Brokalaki EI, et al. Left 
hepatic trisectionectomy for hepatobiliary malignancies. J Am Coll Surg 2006; 203:311-321. 
10. Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right hepatectomy: 
prospective clinical trial. Ann Surg 2003; 237:208-217. 
11. Shindoh J, Tzeng CW, Aloia TA, et al. Optimal Future Liver Remnant in Patients Treated with 
Extensive Preoperative Chemotherapy for Colorectal Liver Metastases. Ann 
Surg Oncol 2013. 
12. Wicherts DA, Miller R, de Haas RJ, et al. Long-term results of two-
stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg 2008; 
248:994-1005. 
13. Tsai S, Marques HP, de Jong MC, et al. Two-stage strategy for patients with extensive 
bilateral colorectal liver metastases. HPB (Oxford) 2010; 12:262-269. 
14. Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of 
advanced colorectal liver metastases: response-based selection and complete resection 
define outcome. J Clin Oncol 2011; 29:1083-1090. 

 
 
 
11 
                       
Headquarters | Royal Free London NHS Foundation Trust | UK | LiverGroup.org 
  
15. Schadde E, Ardiles V, Robles-Campos R, et al. Early survival and safety of ALPPS: first 
report of the International ALPPS Registry. Ann Surg 2014; 260:829-836; discussion 836-
828. 
16. Dokmak S, Belghiti J. Which limits to the "ALPPS" approach? Ann Surg 2012; 256:e6; author 
reply e16-17. 
17. Aloia TA, Vauthey JN. Associating liver partition and portal vein ligation for 
staged hepatectomy (ALPPS): what is gained and what is lost? Ann Surg 2012; 256:e9; 
author reply e16-19. 
18. Azoulay D, Lim C, Salloum C, et al. Complex Liver Resection Using Standard Total Vascular 
Exclusion, Venovenous Bypass, and In Situ Hypothermic Portal Perfusion: An Audit of 77 
Consecutive Cases. Ann Surg 2015; 262:93-104. 
19. Hernandez-Alejandro R, Bertens KA, Pineda-Solis K, et al. Can we improve the morbidity 
and mortality associated with the associating liver partition with portal vein ligation for 
staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases? 
Surgery 2015; 157:194-201. 
20. Alvarez FA, Ardiles V, de Santibanes M, et al. Associating liver partition and portal vein 
ligation for staged hepatectomy offers high oncological feasibility with adequate patient 
safety: a prospective study at a single center. Ann Surg 2015; 261:723-732. 
21. Emilsson L, Lindahl B, Koster M, et al. Review of 103 Swedish Healthcare Quality Registries. 
J Intern Med 2015; 277:94-136. 
22. Aldrighetti L, Belli G, Boni L, et al. Italian experience in minimally invasive liver surgery: a 
national survey. Updates Surg 2015; 67:129-140. 
23. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical 
complications: five-year experience. Ann Surg 2009; 250:187-196. 
24. Raptis DA, Mettler T, Fischer MA, et al. Managing multicentre clinical trials with open source. 
Inform Health Soc Care. 2014 Mar;39(2):67-80.