European Journal of Cardiovascular Medicine

Gallbladder cancer (GBC) represents a relatively rare but highly lethal malignancy of the gastrointestinal tract. Its incidence varies globally, with marked geographic heterogeneity: high prevalence is reported in Northern India, Pakistan, Chile, and certain Eastern European regions, while it remains comparatively uncommon in Western countries. In India, GBC accounts for approximately 10% of all gastrointestinal cancers and disproportionately affects women.

One of the most significant challenges in GBC management is its late presentation. Symptoms such as right upper quadrant pain, dyspepsia, nausea, and weight loss overlap substantially with benign conditions like chronic cholecystitis and gallstones. Consequently, most cases are diagnosed at advanced stages, when curative resection is often impossible. The five-year survival for advanced GBC remains dismal at less than 10%, underscoring the need for early and reliable diagnostic markers.

Role of Imaging in Gallbladder Pathology

Ultrasonography (USG) is the first-line imaging modality for gallbladder evaluation. It is inexpensive, widely available, and highly sensitive for gallstones and gallbladder wall abnormalities. Gallbladder wall thickening (GBWT) is a frequent finding, but its interpretation remains challenging. It can occur in both benign and malignant conditions, including:

• Benign causes: Chronic cholecystitis, acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis (XGC), hepatitis, portal hypertension.
• Malignant causes: Gallbladder carcinoma infiltrating the wall, polypoid lesions with mural thickening.

While focal, irregular, and asymmetric thickening is more suspicious for malignancy, diffuse thickening may be seen in both benign and malignant conditions. Thus, GBWT alone cannot provide a definitive diagnosis, but it may serve as a useful screening marker for early suspicion.

Gallbladder Wall Thickness as a Predictor of Malignancy

Histopathology remains the gold standard for diagnosing GBC. However, there is increasing interest in preoperative predictors to guide early intervention. Several studies have highlighted the correlation between gallbladder wall thickness and malignancy risk. A thicker gallbladder wall, particularly when exceeding 10 mm, has been linked with higher likelihood of carcinoma. However, overlap with inflammatory conditions complicates interpretation.

Given the endemic nature of GBC in Northern India and the increasing number of cholecystectomies being performed, it is crucial to assess whether GBWT can serve as a reliable predictive marker in distinguishing malignant from benign disease in our population.

Aim of the Study

This prospective observational study was conducted to evaluate:

1. The significance of gallbladder wall thickness measured by ultrasonography as a predictor of malignancy.
2. The sensitivity and specificity of various cutoff values of GBWT.
3. The correlation of GBWT with histopathological outcomes and demographic features.

REVIEW OF LITERATURE

Gallbladder carcinoma has been the subject of extensive research, especially in high-incidence regions. Historical studies from North India and South America have consistently reported high female predominance and strong association with gallstones.

Pathogenesis: Chronic irritation and inflammation, often due to gallstones, lead to metaplasia, dysplasia, and ultimately carcinoma. Other risk factors include porcelain gallbladder, anomalous pancreaticobiliary duct junction, and genetic predispositions.

Imaging Correlates:

• USG: First-line, showing wall thickening, mass lesions, or mucosal irregularity.
• CT/MRI: Useful for local invasion and staging.
• PET-CT: Helpful in detecting metastasis.

Wall Thickness:

• Diffuse symmetric thickening <4 mm is usually benign.
• Irregular asymmetric thickening >10 mm raises suspicion of carcinoma.
• Studies by Furuhashi et al. and Levy et al. confirmed that marked thickening, especially when associated with focal mass, predicts malignancy with high specificity.

Overlap with Benign Conditions:

Xanthogranulomatous cholecystitis (XGC) remains the most notorious mimic of carcinoma, both radiologically and intraoperatively. Histopathology is often required to differentiate.

Regional Studies:

In Kashmir and Eastern India, studies have emphasized the predictive role of GBWT. However, variability in cutoff values (ranging from 5 to 12 mm) highlights the need for population-specific validation.

Study Design: Prospective observational study.

Duration: 18 months (Jan 2023 – Jun 2024).

Setting: Department of General Surgery, Government Medical College.

Sample Size: 76 patients undergoing cholecystectomy.

Inclusion Criteria :

• Patients with symptomatic gallbladder disease scheduled for cholecystectomy.
• Preoperative USG performed with documented gallbladder wall thickness.
• Patients consenting for participation.

Exclusion Criteria:

• Acute acalculous cholecystitis.
• Patients with chronic liver disease, portal hypertension, or systemic causes of GBWT.
• Patients unfit for surgery.

Data Collection

• Demographics: age, sex, risk factors.
• Clinical features: duration of pain, jaundice, weight loss.
• USG findings: wall thickness, gallstones, mass lesions.
• HPE reports post-cholecystectomy.

Statistical Analysis:

• Continuous variables expressed as mean ±
• Chi-square test for categorical variables.
• Receiver Operating Characteristic (ROC) curve used to determine optimal GBWT cutoff for malignancy prediction.
• p < 0.05 considered significant.

Demographics

• Mean age: 52.6 years (range 32–74).
• Female predominance: 68% (F:M = 2.1:1).
• Most patients presented with right upper quadrant pain and dyspepsia.

Histopathological Diagnosis

• Benign lesions: 59 cases (chronic cholecystitis 41, XGC 10, adenomyomatosis 8).
• Malignant lesions: 17 cases (adenocarcinoma).

Gallbladder Wall Thickness

• Mean GBWT (benign): 5.2 ± 8 mm.
• Mean GBWT (malignant): 12.4 ± 6 mm (p < 0.001).

ROC Analysis

• Optimal cutoff: 10 mm.
• Sensitivity: 82.3%.
• Specificity: 88.1%.
• AUC: 0.91 (excellent diagnostic accuracy).

False Positives/Negatives

• False positives: mostly XGC (radiologically indistinguishable).
• False negatives: early GBC with subtle thickening.

This study highlights the significance of gallbladder wall thickness (GBWT) as a predictive marker of malignancy in an endemic region.

Correlation with Literature

Our findings are consistent with earlier Indian studies (Nundy et al., Kapoor et al.) which demonstrated that wall thickness >10 mm is highly suggestive of malignancy. The sensitivity and specificity values in our study (82% and 88%) are comparable to international studies, underscoring the robustness of this parameter.

Clinical Relevance

• Screening: In endemic regions, patients with marked GBWT (>10 mm) on routine USG should be considered high-risk.
• Surgical Planning: Suspicious GBWT may warrant frozen section or extended resection at time of surgery.
• Resource-Limited Settings: Since CT and MRI may not be available everywhere, USG-based markers like GBWT are invaluable.

Challenges

• Overlap with XGC: Differentiation remains difficult, often requiring intraoperative assessment.
• Operator Dependency: USG interpretation varies with radiologist expertise.
• Need for Multimodal Assessment: GBWT should ideally be combined with other predictors (polyp size, mucosal irregularity, Doppler vascularity).

Limitations

• Small sample size (n=76).
• Single-center study.
• Short follow-up; survival outcomes not assessed.

Future Directions

• Larger multicenter trials to validate cutoff.
• Integration with biochemical and molecular markers.
• Role of elastography and contrast-enhanced USG in refining diagnosis.

Gallbladder wall thickness measured by ultrasonography is a valuable, non-invasive predictor of gallbladder malignancy. A cutoff of 10 mm demonstrated high sensitivity and specificity in distinguishing malignant from benign disease. While false positives (mainly XGC) remain a diagnostic challenge, the parameter holds strong promise as a screening tool in high-incidence regions like Northern India.

Incorporating GBWT into preoperative assessment may facilitate earlier detection, better surgical planning, and improved patient outcomes.

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3. Levy AD, et al. Imaging of gallbladder carcinoma. Radiographics.
4. Furuhashi N, et al. Gallbladder wall thickening and its clinical significance. World J Surg.
5. Roa I, et al. Gallbladder carcinoma in Chile: clinicopathological features. Ann Surg.
6. Wistuba II, et al. Molecular pathways in gallbladder carcinoma. Cancer.
7. Shukla VK, et al. Epidemiology of gallbladder cancer in Northern India. J Surg Oncol.