Every year, many patients undergo weight-loss (bariatric) surgery. While this surgery leads to significant and intended weight loss, it also increases the risk of developing gallstones or other gallbladder problems.

Approximately one in five patients later requires a second operation to remove the gallbladder. This type of surgery carries a higher risk of complications and reoperations compared with gallbladder surgery performed in the general population.

Preventive treatment may help reduce this risk. One option is medical treatment with Ursochol, which has been shown to lower the risk of developing gallstones after bariatric surgery. However, this treatment is only effective in patients who have not already developed gallstones before surgery.

This means patients need a reliable preoperative ultrasound examination of the gallbladder. Unfortunately, performing ultrasound can be technically challenging in patients with obesity, making it harder to detect small stones or other abnormalities.

The goal is therefore to improve the examination of the gallbladder in patients undergoing bariatric surgery in order to better identify who may benefit from preventive treatment.

The study

The investigators are comparing two types of ultrasound examination of the gallbladder:

• Standard ultrasound performed on the outside of the abdomen using a handheld probe.
• Laparoscopic ultrasound performed during bariatric surgery using a small ultrasound probe placed inside the abdomen, typically placed on the liver near the gallbladder.

It is of interest to find out whether the ultrasound performed during surgery finds more:

• Gallstones
• Sludge
• Small stones (microlithiasis)
• Thickening of the gallbladder wall

By improving detection, the investigators aim to better guide preventive treatment and reduce the need for future gallbladder surgery.

1. TITLE Transabdominal and Laparoscopic Ultrasound in a Bariatric Setting

2. BACKGROUND AND RATIONALE

   2.1 Clinical Background Bariatric surgery is an established and effective treatment for severe obesity. In Denmark, approximately 2,000 bariatric procedures are performed annually. These procedures result in significant and intended weight loss and improvement in metabolic comorbidities. However, rapid weight loss is associated with an increased risk of gallstone formation.

   Gallstone disease is one of the most common postoperative complications following bariatric surgery. Approximately 10% of patients undergo cholecystectomy within two years after surgery, increasing to up to 20% within ten years. Importantly, cholecystectomy in patients who previously underwent bariatric surgery is associated with:

   • Increased risk of surgical complications

   • Higher rates of reoperation

   • More technically complex procedures
   • Increased risk of bile duct injury In patients with Roux-en-Y gastric bypass, management of biliary tract disease is particularly challenging due to altered gastrointestinal anatomy, which complicates endoscopic access (e.g., ERCP).

   2.2 Preventive Treatment and Diagnostic Challenge Prophylactic treatment with ursodeoxycholic acid (Ursochol) has been shown to significantly reduce the risk of symptomatic gallstone disease in the first two years after bariatric surgery.

   However:

   • Ursochol is only effective in patients who do not already have gallstones.

   • Therefore, accurate preoperative detection of gallstones is essential.

   Conventional transabdominal ultrasound (TAUS) is the standard imaging modality for gallbladder evaluation. However, in patients with severe obesity:

   • Ultrasound penetration is limited
   • Image quality may be reduced
   • Small stones and sludge may be overlooked
   • Sensitivity may be as low as 62-68%

   Thus, diagnostic uncertainty may lead to:

   • Under-treatment (missed stones)

   • Over-treatment (inappropriate prophylaxis)

   • Inconsistent national implementation

   2.3 Rationale for Laparoscopic Ultrasound (LUS)

   Laparoscopic ultrasound (LUS) allows:

   • Direct placement of the probe on the liver surface

   • Shorter acoustic distance

   • Higher image resolution

   • Potentially improved detection of subtle pathology

   • Fewer hospital visits for the patients prior to surgery

   Only one prior study has directly compared TAUS and LUS in this population. That study suggested higher overall pathology detection with LUS, but lacked:

   • Histological confirmation

   • Sample size justification

   • Assessment of microlithiasis
   • Gallbladder wall measurements
   • Formal evaluation of interobserver agreement within each ultrasound modality

   Therefore, a well-designed prospective paired diagnostic study is warranted.

3. OBJECTIVES

3.1 Primary Objective To compare the diagnostic detection rate of gallbladder pathology between transabdominal ultrasound (TAUS) and laparoscopic ultrasound (LUS) in patients undergoing bariatric surgery.

3.2 Secondary Objectives

1. To evaluate interobserver agreement within TAUS and LUS examinations
2. To compare examination time between modalities
3. To assess image quality
4. HYPOTHESES

1. Laparoscopic ultrasound detects significantly more gallbladder pathology than transabdominal ultrasound.

2. LUS has lower interobserver variability compared to TAUS.

5. STUDY DESIGN Prospective observational diagnostic comparative study with paired within-patient design.

Each participant undergoes:

• Two independent TAUS examinations
• Two independent LUS examinations

All examinations are performed blinded and independently.

No randomization is performed.

No experimental interventions are introduced.

6. STUDY PROCEDURES

6.1 Preoperative Phase

Participants undergo:

• Two transabdominal ultrasounds

• Performed on the same day
• By two independent radiologists/sonographers
• Blinded to each other's findings

6.2 Intraoperative Phase

During planned bariatric surgery:

• Two surgeons independently perform laparoscopic ultrasound

• Probe placed directly on liver surface

• Examinations blinded

• Adds 5-10 minutes to procedure

  7. STATISTICAL ANALYSIS PLAN

7.1 Primary Analysis McNemar's test for paired binary outcomes.

Significance level: 0.05 (one-sided)

Power: 90%

7.2 Sample Size Calculation Sample size was calculated for a paired binary comparison of the composite gallbladder pathology outcome between transabdominal ultrasound (TAUS) and laparoscopic ultrasound (LUS) using a one-sided McNemar test (α=0.05, power=90%). The sample size was calculated in two ways. Under one model, we assumed the detection rates of 25% for TAUS and 35% for LUS with an estimated between-modality correlation of 0.70. In the second model, we assumed discordant proportions of 0.10 (TAUSnegative / LUSpositive) and 0.01 (TAUSpositive / LUSnegative). Approximately in both models, the required sample size was 117 evaluable paired patients; allowing for 10% dropout/non-evaluable cases, we will enroll 130 patients in total.

7.3 Secondary Analyses • Interobserver agreement: Cohen's kappa

• Subgroup analyses (BMI strata, bariatric surgery)

All analyses conducted in STATA.

8. ETHICAL CONSIDERATIONS

8.1 Risk Assessment Both TAUS and LUS examinations are well known diagnostic modalities without any known risk profile. The LUS procedure will add 5-10 minutes of additional surgery, which seems reasonable.

Overall, the risk of the examinations are considered minimal.

8.2 Potential Benefits • Improved diagnostic precision

• Better patient selection for preventive treatment

• Reduced need for future gallbladder surgery

• Simpler ultrasound examinations

  9. DATA MANAGEMENT

• Data stored in secure SharePoint research environment and REDCap Systems

• GDPR compliant

• Restricted access

• Registered internally at hospital

  10. DISSEMINATION

Results will be:

• Published regardless of outcome

• Submitted to peer-reviewed journals

11. FUNDING

• Part of a PhD program

• No funding from private companies

• Additional funding sought from regional and national foundations

12. EXPECTED IMPACT

If LUS demonstrates superior diagnostic performance:

• It may guide selective prophylactic therapy
• It may reduce long-term gallbladder morbidity
• It may standardize diagnostic workup

This study has direct translational relevance to clinical practice.

Inclusion Criteria:

• Age ≥18 years
• Scheduled for bariatric surgery
• Able to provide informed consent

Exclusion Criteria:

• Previous cholecystectomy
• Previous biliary surgery
• Previous liver surgery
• Inability to provide informed consent

Individual participant data will not be shared due to national data protection regulations and institutional restrictions.