Protocol
Abstract
Aim: Define benchmark outcomes in adult liver transplantation
Design: Multicenter retrospective cohort study
Primary outcome measure: Morbidity as defined by the Clavien-Dindo classification for surgical complications and the comprehensive complication index at discharge, 3, 6 and 12 months
Hospital eligibility: High volume centers (> 50 liver transplantation/year), conducting a prospective database as well as previous publications critically reporting on their outcome
Inclusion criteria: Adult patients (>18 years) who underwent brain death cadaveric liver transplantation from 01.01.2010 to 31.12.2014.
Exclusion criteria: Multiorgan transplantations, second recipients in domino transplantations, DCD grafts and split/partial grafts, previous major abdominal surgery, portal vein thrombosis, LabMELD ≥ 30, intubation before transplantation, acute graft failure, super-urgent listing.
Data collection Deadline: August 2016
Introduction
With the growing complexity and costs of modern surgical practice, quality assessment becomes mandatory. The notion of quality and quality assessment is widely recognized and used in the world of business and manufacturing. A possible tool of quality assessment is benchmarking. Benchmarking is a process of measuring performance in order to enable for outcome comparison and improvement within a specific domain. In the surgical community, however, such standard outcome measures and multicenter comparison of results are not available and benchmarking for the best possible results for specific procedures is lacking.
Recently, a first landmark study defining benchmark outcomes for liver resection has been presented at the 2016 ASA meeting in Chicago. (1)
Since liver transplantation (LT) is a high-risk procedure associated with high morbidity and 10-20% of 1-year mortality, quality assessment is of major importance. Up to date no data is available on the best achievable results in liver transplant procedures. To identify the best possible outcome i.e. benchmarking, data from high volume centers in low risk patients will be thoroughly analyzed. These benchmark outcomes will serve as <<negative controls >> for comparison with single center outcomes, high-risk patients and future developments.
Policy Securing
Confidential center specific data: No center-specific data will be published. Instead, all complications or adverse outcomes will be anonymously reported, as fractions of the total study population. Each center, of course, will be free to publish their own data, as they wish.
Authorship: No data will be submitted or published without authorization from each participating center. Each center will be represented by two co-authors. In the ideal case there will be one junior author who will coordinate data collection with Dr. Xavier Muller (coordinator of the study from Zurich). If necessary, three authors may be included for one center in the authorship list.
Further use of cohort data: Future studies based on the collected data will hopefully emerge from this multicenter study e.g. comparing outcomes in re-transplanted patient with the benchmark outcomes.
Methods
Objective:
To conduct a retrospective multicenter cohort study to define benchmark criteria for best achievable outcomes in deceased donor liver transplantation (LT) to serve as negative controls in quality assessment. The benchmark criteria will be derived from postoperative mortality and morbidity as well as graft function and survival.
Aims:
The primary aim is to define benchmark outcomes by identifying post LT complications according to the Clavien-Dindo classification for surgical complications (2,3) and the comprehensive complication index CCI (4) at discharge, 3, 6 and 12 months.
The secondary aims are:
- One-year patient and graft survival
- Assess graft function according to different criteria (6-10)
Time period:
- The study will cover a 5-year period, from 01.01.2010 to 31.12.2014.
Hospital inclusion criteria
- Single centers performing > 50 liver LT per year
- Centers having a prospective database from which most of the data can be extracted
- All centers are required to have previous publications critically reporting on their outcome
Patient eligibility
Inclusion criteria
- Adult patients (>18 years) who underwent brain death cadaveric liver transplantation.
Exclusion criteria
- LabMELD ≥ 30
- Re-transplantation
- Previous major abdominal surgery1
- Complete and partial portal vein thrombosis
- Donation after cardiac death grafts (NHBD)
- Acute liver failure/super-urgent listing
- Intubation at the time of transplant
- Multiorgan transplantation
- Living donor transplantation including second recipients in domino transplantation
- Split or partial grafts
1Note 1: previous abdominal surgery as exclusion criteria:
- Only patients who underwent previous upper GI surgery, major lower GI surgery and laparotomy should be excluded.
- Patients with laparoscopic appendectomy, pelvic or inguinal surgery ( Lichtenstein procedure, hysterectomy...) should be included
Note 2: Patients who were transplanted before the study period and are re-transplanted during the study period should be excluded. If patients are re-transplanted during the study period this should be indicated as graft failure. The follow-up after re-transplantation should not be analyzed in this study.
Outcome Measures
Primary outcome measure
The primary outcome measure is identifying post LT complications according to the Clavien-Dindo classification for surgical complications (2,3) and the comprehensive complication index CCI (4) at discharge, 3, 6 and 12 months.
This requires the patient to have a documented post-transplantation follow-up during 12-months in the center conducting the study. Every complication has to be assessed according to the Clavien-Dindo classification. The corresponding CCI will be calculated by the coordinating center in Zurich.
Secondary outcome measures are:
- Assessment of one-year patient and graft survival
- Pre-operative patient characteristics including the MELD score in order to stratify patient according to pre-transplantation risk
- Collection of post-transplantation biochemical data in order to characterize graft function
Governance
Data will be collected via a secure online webpage, provided by the University Hospital of Zurich. This website uses a data entry management system (DEMS) to meet international standards for online databases including fully anonymized data. Data will not be published with hospital identifiers.
Collecting data
Local collaborators: Most hospitals will have two local investigators: a senior and a junior investigator. The junior collaborator will be in regular contact with the study coordinator in Zurich. The junior investigator will be responsible for:
- Gaining local research ethics approval
- Identifying and including all eligible patients
- Accurately collect baseline and follow-up data
- Submit data to the online DEMS database
References
- Rössler F, Sapisochin G, Song G, et al. Defining Benchmarks for major liver surgery. A multicenter analysis of 5202 living liver donors. Ann Surg in press.
- Dindo D, Demartines N, Clavien PA. Classification of Surgical Complications. A New Proposal with Evaluation in a Cohort of 6336 Patients and Results of a Survey. Ann Surg. 2004;240:205-213.
- 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.
- Slankamenac K, Graf R, Barkun J, et al. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258:1-7.
- Dutkowski P, Schlegel A, Slankamenac K, et al. The use of fatty liver grafts in modern allocation systems: risk assessment by the balance of risk (BAR) score. Ann Surg. 2012;256:861–868
- Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–724
- Balzan S, Belghiti J, Farges O, et al. The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242:824–828.
- Mullen JT, Ribero D, Reddy SK, et al. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. J Am Coll Surg. 2007;204:854–862.
- Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant. 2005;5:2605-2610
- Olthoff MK, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010; 16:943-949.
Appendix A: Data fields
Note: Day of surgery is defined as post-operative day 0
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Patient ID. Only you will have access to this secure field. If you don’t have hospital Ids at your center, enter a identifying number here that you can match to the patient (e.g. 01, 02,)
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Recipient liver disease
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1
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Recipient Age
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> 18 years
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2
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Underlying liver disease
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At the time of transplant
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3
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If hepatocellular carcinoma indicate the largest diameter of the biggest viable tumor lesion
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In cm at the time of transplant (after pre-treatment if applies)
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4
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If multifocal hepatocellular carcinoma, indicate the total number of viable tumor lesions
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At the time of transplant (after pre-treatment if applies)
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Recipient pre-transplant
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6
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Lab MELD: Model for End stage Liver Disease using the following criteria:
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Ranging from 6-40
Important to calculate using the most recent values before transplant including the following
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7a: INR (International Normalized Ratio)
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Prior to transplant
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7b: Bilirubin (μmol/l)
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Prior to transplant
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7c: Creatinine (μmol/l)
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Prior to transplant
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7d: Renal replacement therapy at least twice in the week prior to transplant
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Yes/No
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7
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RRT (renal replacement therapy) during the last 4 weeks before transplant
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Yes/No
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Donor characteristics
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8
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Donor age
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In years
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9
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Macro-steatosis of the graft
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In % as stated by the pathologist on biopsy if not available as estimated by the surgeon during the procedure
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Transplant procedure
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10
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Cold ischemia time of the graft
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In hours
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11
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Operation duration
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In minutes
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12
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Number of intraoperative blood transfusions
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In numbers of red blood cell units
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13
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INR (International Normalized Ratio) on postoperative day 5
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14
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INR (International Normalized Ratio) on postoperative day 7
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15
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INR (International Normalized Ratio) >2 on 3 consecutive days within the first week of surgery
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Yes/No
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16
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Bilirubin on postoperative day 5
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In μmol/l
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17
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Bilirubin on postoperative day 7
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In μmol/l
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18
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Bilirubin > 100 μmol/l (5,9 mg/dl)
on 3 consecutive postoperative days during the first week
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Yes/No
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19
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ALT (Alanine aminotransferase) peak during the first postoperative week
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In IU/l
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20
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Creatinine peak within the first 7 post-transplant days
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Highest value in μmol/l
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21
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Renal replacement therapy (RRT) after transplant until discharge
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Yes/No
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22
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If RRT: Duration of post-transplant RTT
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In days
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23
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Encephalopathy grade III or IV on 3 consecutive post op days within the first 7 days of surgery
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Grad III: marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli
Grade IV: comatose, unresponsive to pain, decorticate or decerebreate posture
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Recipient complications
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24
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Bleeding complications
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e.g. intra-abdominal bleeding, hematuria…
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25
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Biliary complications
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e.g. stricture, leakage, bilioma…
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26
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Infection
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e.g. wound infection, intra-abdominal infection, pneumonia…
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27
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Ascites
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e.g. paracentesis, hypoalbuminemia…
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Recipient outcome
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28
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Length of hospital stay
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In days from the date of transplant
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29
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Length of intensive care unit stay (ICU)
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In days
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Recipient complications within the 12 months after transplant
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Complications until
discharge excluded
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30
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Readmission due to complication
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In-hospital stay > 24h within the first 30 days after discharge in direct relation to the cited complication
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Graft function follow up
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31
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Graft loss
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Death or re-transplantation
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32
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Cause of graft loss
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e.g. arterial thrombosis, acute rejection…
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33
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Days from transplant to graft loss
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In days: From the day of transplant until graft loss
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34
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Re-transplantation
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After graft loss, yes/no
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Recipient follow up
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35
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Recipient status at last FU
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Death/alive
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36
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Patient survival in days
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If death occurred: how many days after transplantation
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37
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Creatinine after 1 year
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In μmol/l
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38
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Glomerular Filtration rate after 1 year (GFR)
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GFR 1 year after the transplant procedure calculated by the Cockroft-Gault formula/sites/default/files/OLTB_Protocol_v6.pdf
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If you are a member of the collaborators of this study, please first login to this website to access the study documents and submit your cases.


