5 Things you should know about Gallbladder Cancer Management

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. It’s also the most aggressive gastrointestinal malignancy with five-year survival rate between 5-15% in relation to advanced stage at diagnosis. GBC can be suspected preoperatively or most commonly as an incidental finding on surgery or pathologic review. Current available systemic therapy is not effective in the majority of patients with distant metastases and surgical R0 resection is the only potential curative treatment.

SEPIDEMIOLOGY and PATHOLOGY

Worldwide incidence of GBC is less than 2/100,000 individuals but has a prominent geographic variability that correlates with the prevalence of cholelithiasis (> 10/100,000 cases in Chile, Northern India and Japan). The average age at diagnosis is 65 years old with female predisposition (3:1 ratio). Cholelithiasis is considered a primary etiological factor in GBC resulting in chronic mucosal inflammation over several years that may lead to dysplasia and malignant transformation. Progression from adenoma to carcinoma may also have a role in pathogenesis given the increased incidence of adenocarcinoma in gallbladder polyps larger than 1cm (indication for cholecystectomy).

PRESENTATION AND WORKUP

1·GALLBLADDER MASS OR DISEASE SUSPICIOUS FOR GBC:

The initial workup includes a cross-sectional study with CT and/or MRI. Liver function tests, assessment of hepatic reserve and CEA and CA19.9 testing. Laparoscopic staging is recommended priori laparotomy for all instances of suspected or proven gallbladder cancer. Routine biopsy is not required.

– In early staged T1a tumors a simple cholecystectomy is an adequate treatment. – For T1b and T2 tumors an optimal resection requires an extended cholecystectomy + and hepatoduodenal lymphadenectomy of at least 6 lymph nodes – For locally advanced disease (T3-T4), selected patients with good performance status and without distant disease could benefit for radical surgery with en bloc resection of involved with strong consideration for neoadjuvant therapy involved in clinical trials.

2· INCIDENTAL GBC AT SURGERY

Intraoperative discovery of a GBC should prompt closure and subsequent referral to a hepatobiliary center. Other opinions support that if there is persuasive clinical evidence and an experienced surgeon is available, a definitive resection should be performed.

3· INCIDENTAL GBC AT PATHOLOGIC REVIEW

Consider pathologic re-review by an hepatobiliary pathologist expert. Staging evaluation with cross-sectional imaging should be completed. Laparoscopic staging prior to laparotomy is recommended in incidental GBC as it could identify about 20% of patients with distant disease.

– Re-resection between 4 and 8 weeks is indicated for T1b, T2 and T3 incidentally discovered GBC, unless contraindicated by advanced disease or poor performance status. – T1a lesions may be observed since these tumors don’t penetrate the muscle layer and long-term survival approaches 100% with simple cholecystectomy.

Role of neoadjuvant and adjuvant therapy. Scarce high-quality data currently exists for the optimal systemic strategy for gallbladder adenocarcinoma.

– Patients with preoperatively staged T3-T4 and lymph node disease should be considered for clinical trials studying the efficacy of neoadjuvant chemotherapy – Adjuvant therapy with chemotherapy and/or chemoradiotherapy should be offered following R0 resection of ≥ T2 and positive node GBC and if microscopically positive surgical margins.

Palliative therapy for unresectable metastatic disease. The affection of liver or peritoneal metastases, malignant ascites, metastases to lymph nodes beyond locoregional nodes (in the celiac axis or aortocaval groove), extensive involvement of the hepatoduodenal ligament, or encasement or occlusion of major vessels are considered unresectable. The mainstay of palliative treatment in GBC is maintenance of adequate biliary drainage, nutrition and local compressive symptoms. Chemotherapy can provide effective palliation treatment.