Identification of Predictive Factors of Incidentally Detected Gallbladder Cancer and Prospective Validation of a Scoring System to Allow Selective Histological Analysis of the Gallbladder

This is a cross-sectional study of prospectively identified (identified in advance) patients undergoing routine gallbladder surgery in the United Kingdom (UK). It will be undertaken in two phases and has an adaptive design. This means that the results of the first phase could affect the design of the second phase.

The first phase includes a parallel, interview based study which will explore the risk of incidental Gallbladder Cancer (iGBC) and establish whether Selective Histological Analysis (where gallbladders are chosen for post-operative tests based on their individual risk of iGBC) is acceptable to a representative cohort.

The primary objective of this study is to develop and validate a diagnostic scoring system for iGBC in UK patients undergoing routine gallbladder surgery. There are two similar scores in existence, however they have been conducted in a way which means that their data may be skewed, because they were conducted in countries which already use selective histological analysis and have very different pathways to cholecystectomy when compared to the UK. The investigators therefore need to build a new, UK dataset, and the most reliable way to do this is to intentionally collect all of the required data from a new set of patients. Often this can be done using patients who have already been treated - called retrospective (looking backwards) data collection. However, to be a high-quality dataset requires each patient to consistently have a complete set of data, and the investigators know that retrospective studies often lead to missing data points. Additionally, intraoperative findings are always recorded on an operation note, but not always in a consistent way. By collecting data on patients who will be treated during a future study period (prospective data collection), the investigators can ask for these findings to be recorded in a way which is standardised, so they can be reliably compared between surgeons and hospitals. The investigators have therefore elected to undertake a prospective study of patients undergoing routine gallbladder surgery.

To identify risk factors for a disease, a sample size which would be expected to give rise to ten "events", or diagnoses, of interest is typically felt to be required. As iGBC is thought to be present in about one in every 500 gallbladder operations, this gives a sample size of 5,000 patients to identify risk factors. However, to develop a model of the factors which cause the disease, from which a diagnostic scoring system can be produced, the expected number of diagnostic parameters needed, which may be included in the scoring system, has to be considered. A diagnostic parameter is a variable, for example the biological sex of a patient, and each variable is counted at least once. When a variable has more than two potential options, for example a patient's ethnicity, each additional option is counted as an extra parameter. The previous diagnostic scores have used 3-4 diagnostic parameters, however they have lacked the nuance required of the test. Several of the known and suspected risk factors have more than one potential option, and after discussion, it was felt that allowing for 20 diagnostic parameters was realistic. With their statistician, the investigators have calculated a minimum number of fully completed patient records of just under 21,000. It is unrealistic to expect that every record will be fully completed, and in line with convention the investigators have planned for 80% of records to be fully completed. They provisionally, therefore, expect to require 26,245 patient records to achieve statistical power and will provisionally target 30,000 to allow expansion as the result of necessary variation from expected findings which may become evident after the feasibility phase.

Attempting to conduct a study of up to 30,000 patients without proof of concept could result in a lot of effort without success. Therefore, the investigators have designed a two-stage study. The first stage will test the feasibility of the whole study and will consist of a pilot, or "dry run" of the proposed methodology. This dry run will be conducted across 8 surgical units, from within 7 organisations, and over 6 months will collect data from as many as 500 patients. This will allow the investigators to assess whether they can recruit enough patients, quickly enough from the number of participating sites which are involved to be able to conduct the full study within the proposed timeframe. It will also establish whether the data which is being collected is sufficiently complete (i.e. high quality) to be useful if collected from all the patients needed to develop the diagnostic score. Finally, the investigators will be able to confirm whether the population they are testing has rates of incidental cancer and other changes which are in line with published and previously observed rates. Alongside this pilot study, the investigators will conduct an interview based study to establish how patients and relevant professionals think about the risk of incidental cancer in routine cholecystectomy, and what the participants perceive the barriers to and acceptability of selective histological analysis is.