What is the most probable diagnosis for a patient with right upper quadrant (RUQ) pain, fever, and obstructive jaundice?

Gallbladder Adenocarcinoma: Diagnosis and Management in Advanced Disease

For a patient with RUQ pain, fever, obstructive jaundice, weight loss, malaise, fatigue, night sweats, and peritoneal nodules, the most probable diagnosis is gallbladder adenocarcinoma (advanced). 1

Clinical Features Supporting Gallbladder Cancer Diagnosis

• Right upper quadrant pain is a common presenting symptom of gallbladder cancer, particularly in advanced cases where the disease has spread beyond the gallbladder 1
• Systemic manifestations including weight loss, malaise, fatigue, and night sweats are typical of advanced gallbladder malignancy 1
• Obstructive jaundice with elevated bilirubin and other liver function tests indicates biliary obstruction, which commonly occurs with advanced gallbladder cancer 1, 2
• The presence of peritoneal nodules is highly suggestive of gallbladder cancer with peritoneal spread 1
• Approximately 32% of patients with severe jaundice have obstructive jaundice, with malignancy being the most common cause 2

Differential Diagnosis

• Klatskin tumor (hilar cholangiocarcinoma): Typically presents with dilated intrahepatic bile ducts and a contracted rather than distended gallbladder (Courvoisier's law) 1
• Emphysematous cholecystitis: Usually presents with acute severe symptoms and gas in the gallbladder wall, which is inconsistent with the chronic history and presence of peritoneal nodules 1
• Pancreatic head cancer: Would typically present with both dilated intra and extrahepatic biliary radicles with deep jaundice, but the presence of peritoneal nodules is more consistent with gallbladder cancer 1

Management Approach for Advanced Gallbladder Cancer

• For gallbladder cancer with peritoneal spread (stage IV), the recommended approach is palliative management 3, 4
• Preoperative biliary drainage is recommended for patients with significant hyperbilirubinemia (bilirubin > 12 mg/dL according to American College of Radiology, or > 3 mg/dL according to French guidelines) 3
• The drainage approach should be determined by a multidisciplinary team including hepatobiliary surgeons, interventional radiologists, and gastroenterologists 3
• Endoscopic approach with removable plastic stents should be considered first-line for preoperative drainage when technically feasible 3, 5
• Complete staging must be performed before determining definitive treatment, including CT abdomen, MRI/MRCP, and chest radiography 3

Treatment Options Based on Disease Stage

• For unresectable disease with peritoneal spread: Permanent biliary drainage with uncovered metal stents and systemic chemotherapy with gemcitabine plus cisplatin are recommended 3
• For patients with advanced gallbladder cancer who are candidates for treatment, a combined approach of surgery plus chemotherapy provides the best survival benefit 4
• Five-year survival rates for patients with curative intent surgery can reach 63.2%, while those with palliative approaches have significantly worse outcomes 6
• Liver involvement is an independent prognostic factor in gallbladder cancer 6

Important Clinical Considerations

• Biliary drainage carries risks of introducing infection; prophylactic antibiotics should be considered 3, 7
• Prolonged biliary obstruction can cause vitamin K deficiency and coagulopathy, which should be corrected before invasive procedures 3
• Painless jaundice is common in malignant biliary obstruction (66% of cases), whereas painful jaundice is more common in benign conditions 2
• The prognosis for malignant obstructive jaundice is poor, with a 2-year mortality rate of 95% 2

Treatment Algorithm for Advanced Gallbladder Cancer with Peritoneal Spread

1. Confirm diagnosis with histological examination (EUS-guided FNA or biopsy of primary tumor or suspicious lymph nodes) 3
2. Complete staging with CT abdomen, MRI/MRCP, and chest radiography 3
3. Manage obstructive jaundice with biliary drainage (preferably endoscopic) 3, 5
4. For confirmed unresectable disease with peritoneal spread, proceed with:
   • Permanent biliary drainage using uncovered metal stents 3
   • Systemic chemotherapy with gemcitabine plus cisplatin 3
5. Provide supportive care to address symptoms and maintain quality of life 3