The Pro-Chol Study

Cholecystectomy is the surgical removal of the gallbladder and the only definitive treatment for both symptomatic complicated and uncomplicated gallstones. Surgery rates for laparoscopic cholecystectomy have been rapidly rising in European countries the past decades. Over 9000 cholecystectomies were performed in Denmark in 2016. Symptomatic outcomes following surgery have not been with the intended resolution of symptoms and remaining symptoms are reported in about 35% of patients. This indicates clinical challenges in selecting the patients that will benefit the most from surgery.

The quality of symptomatic outcomes following laparoscopic cholecystectomy should be assessed in a Danish population reflecting current clinical practice for selection of patients with symptomatic uncomplicated gallstones for surgery. Development of a clinical prediction tool for pain relief including both patient-reported and readily available objective variables could aid future patient selection and minimize overall health-care costs and unnecessary surgery risk in patients with symptomatic uncomplicated gallstones.

The aim is to perform a prospective assessment of the symptomatic outcomes of elective laparoscopic intended cholecystectomy in patients with symptomatic uncomplicated gallstones and to develop a prediction model for a pain-free state.

This is a prospective observational study that will be performed across the general surgical hospitals in healthcare regions of Denmark. Consecutive consenting patients will be included from each site until required sample size has reached.

Eligible patients will be identified through screening lists of outpatient clinics and of operating theaters. Patients will be approached for consent and data collection at either the outpatient clinical visit where cholecystectomy is scheduled or at a later timepoint before surgery. Follow-up for symptomatic outcome will be performed three months after surgery. Data collection at both study entry and follow-up will include access to the electronic patient record and answering an online patient questionnaire. If patient questionnaires remain unanswered after one week, the patient will be reminded through an online re-invitation. Data collection at entry will also include the patients' medical history and clinicopathological variables. Data will be stored in a purpose-build database in the clinical research platform REDCap.

The study will be run by a steering committee including senior surgeons acting as local investigators from each of the participating centers. The local investigator will ensure completion of data forms and follow-up procedures. An additional collaborator from each center may further be appointed responsible for patient identification and data collection.

This study is purely observational and no alterations to standard patient treatment will be performed.

A prediction model with high internal and external validity requires model development and validation to be performed in two independent sets of data. To ensure this, half of patients will be included for model development and the other half for model validation.

Based on a previous report, 60% (57%) will become pain-free following cholecystectomy. With a prediction model containing up to 12 exposure variables and a parameter to outcome event ratio of 1:20, the required sample size is 400 patients for model development. The total sample size will be 800 patients for both development and validation of the model. It is estimated that each center will identify about 20 eligible patients each month and the required inclusion period is therefore about two to three years. Sample size may be reduced if prediction model includes fewer variables.

• Changes in symptoms following surgery [Time frame: From baseline before surgery to follow-up at three months after surgery]