STUDY PROTOCOL

 OBJECTIVE                                                                                                                                    

To conduct a retrospective multicenter cohort study to define benchmark values for best achievable outcomes following major liver surgery for perihilar cholangiocarcinoma (PHC). A secondary aim will be to identify the minimal follow-up necessary to properly assess morbidity associated with major liver surgery for PHC.

 INTRODUCTION                                                                                                                              

With the growing complexity and costs of modern surgical practice, convincing and unbiased quality assessment becomes mandatory. The notion of 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 have been poorly developed and benchmarking for the best possible results for specific procedures is lacking.

The first landmark study defining benchmark outcomes for liver resection was presented at the 2016 ASA meeting in Chicago and published in Ann Surg (Rössler et al., Ann Surg, 2016). More recently benchmark values were established for liver transplantation (Muller et al., Ann Surg, 2018), esophagectomy (Schmidt et al., Ann Surg, 2017), pancreas surgery (Sánchez-Velázquez et al., Ann Surg, 2019), bariatric surgery (Gero et al., Ann Surg, 2019) and ALPPS (Raptis et al., Ann Surg, 2019).

Major liver resection due to a perihilary cholangiocarcinoma is a high-risk procedure still associated with significant mortality (6-12%) and very high severe morbidity (50-65%) (Franken et al., Surgery, 2019). To identify the best possible outcome (i.e. benchmarking), data from high-volume centers in low risk patients will be analyzed. These benchmark outcomes will serve as “controls” for comparison with any future analyses of biliary liver surgery.

 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 its contributors.

In the ideal case there will be one junior author who will coordinate data collection with Dr. Matteo Mueller and Dr. Eva Breuer (coordinators of the study from Zurich).

Further use of cohort data: Future studies based on the collected data will hopefully emerge from this multicenter study.

METHODS                                                                                                                                       

Benchmark Values:

  1. Mortality
  2. Morbidity
  3. Preoperativ characteristics
    • Volume of FLR
    • PVE yes/no
  4. Operation characteristics
    • Duration of surgery
    • Blood loss
    • R0 resection
    • Number of harvested lymph nodes
    • Right vs. left hepatectomy
  5. Length of stay (ICU), length of stay (hospital)
  6. Readmission
  7. Center characteristic: volume per year
  8. Disease free survival (DFS) and Overall survival (OS) (reported at one year)

Study period

  • 1st Jan 2014-Dec 31st 2018 (5 years)

Center eligibility

  • Consider largest program in the respective countries
  • Min. 10 cases per year or 50 cases within 5 years (i.e. the study period)
  • Published in the area of liver surgery
  • Prospective database available

Patient eligibility (benchmark cases criteria)

Please note that, at this stage, the study will include only the benchmark cases.

Inclusion criteria:

  1. Adults ≥ 18 years
  2. Resectable perihilar cholangiocarcinoma 
  3. Major hepatectomy (right or left hemihepatectomy/trisectionectomy)
  4. No significant co-morbidities (see exclusion criteria bellow)

Exclusion criteria:

  1. Non-resectable lesions
  2. Central bisectionectomy or resection of segments 4/5/8±1)
  3. Distant or intrahepatic metastases (based on final pathology)
  4. Vascular invasion with need of vascular resection (HA or PV). Ad note: cases with PV-resection as part of standard PHC surgery are included
  5. Liver transplantation
  6. PHC with distal extension with need for pancreaticoduodenectomy (PD)
  7. Co-morbidities:
    • ASA ≥ 3
    • BMI ≥ 35 (Sánchez-Velázquez et al., Ann Surg, 2019)
    • Cardiac disease (Tran et al., HPB, 2016)
      • Congestive heart failure (CHF) onset or exacerbation in 30 days prior to surgery
      • History of angina pectoris within 1 month of surgery
      • Myocardial infarct within 6 months prior to surgery
      • History of percutaneous coronary intervention or cardiac surgery.
      • Atrial fibrillation (Kazaure et al., World J Surg, 2015)
      • Ad Note: arterial hypertension is not considered as cardiac disease.
    • Chronic renal failure: ≥ stage 3 (GRF<60ml/min per 1.73 m2 or Creatinine > 1.8 mg/dl or 160 μmol/l)
    • Use of anti-coagulation: Non-vitamin K antagonist oral anticoagulants (NOACs) and Vitamin K antagonist and clopidogrel. Note: patients under Aspirin 100mg should not been excluded (Kristensen et al., Eur Heart J, 2014).
    • Lung disease: chronic obstructive pulmonary disease with FEV1<80% (Fields et al., Surgery, 2016).
    • Diabetes: when use more than 2 oral antidiabetes drugs or insulin

Governance

Data will be collected via a secure; password protected, and encrypted online data management system, provided by the University Hospital of Zurich. This platform uses a data entry management system (DEMS) to meet international standards for online databases including fully anonymous data. Data will not be published with hospital identifiers.

Data Collection

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 coordinators in Zurich (Dr. Matteo Mueller; Dr. Eva Breuer). 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