What is the assessment and management plan for an adult with metastatic non‑small cell lung cancer on pemetrexed, prior pembrolizumab‑induced pancreatitis stopped over a year ago, now presenting with new‑onset jaundice, abdominal distension, leukocytosis, international normalized ratio of 1.47, markedly elevated total and direct bilirubin, alkaline phosphatase, gamma‑glutamyl transferase, modest AST and ALT rise, imaging showing intra‑ and extra‑hepatic biliary duct dilation, a 1.8 cm common hepatic duct, distended gallbladder with sludge, peripancreatic fluid collections without pancreatic duct dilation, moderate ascites, and recent travel to the Philippines?

Assessment and Management Plan for Metastatic NSCLC with Biliary Obstruction

Primary Assessment: Malignant Biliary Obstruction vs. Infectious/Inflammatory Etiology

This patient most likely has malignant biliary obstruction from metastatic lung cancer, though infectious cholangitis from recent Philippines travel and recurrent drug-induced pancreatitis must be excluded urgently. The severe intrahepatic and extrahepatic duct dilation (common hepatic duct 1.8 cm) with markedly elevated cholestatic enzymes (alkaline phosphatase 596, total bilirubin 17.6) and absence of liver lesions on imaging strongly suggests extrinsic compression or infiltration at the porta hepatis rather than intrahepatic metastases 1.

Critical Differential Diagnoses to Address Immediately:

• Malignant biliary obstruction from periportal lymphadenopathy or direct tumor extension is the leading diagnosis given metastatic NSCLC, severe biliary dilation without discrete pancreatic mass, and absence of liver lesions 1
• Acute cholangitis must be ruled out given recent Philippines travel, leukocytosis (12.2), fever assessment needed, and biliary obstruction—obtain blood cultures immediately and assess for Charcot's triad 2
• Recurrent pembrolizumab-induced pancreatitis is less likely given discontinuation over one year ago, but the peripancreatic fluid collections (1.8 cm) warrant consideration, though pembrolizumab-related pancreatitis typically presents within weeks to months of exposure 3, 4
• IgG4-related disease causing both pancreatitis and biliary stricture should be considered given the combination of peripancreatic collections and biliary obstruction 2

Immediate Management (First 24-48 Hours)

Diagnostic Workup:

• ERCP with biliary brushings and biopsy is the definitive next step to establish tissue diagnosis, relieve obstruction, and place biliary stent—this addresses both diagnostic and therapeutic needs simultaneously 2
• Blood cultures × 2 sets before antibiotics to rule out cholangitis given recent travel to endemic area for liver flukes and bacterial cholangitis 2
• Hepatitis A, B, C, and E serologies given Philippines travel where hepatitis E is endemic and can cause acute hepatitis with cholestasis 2
• IgG4 levels to evaluate for IgG4-related sclerosing cholangitis, which can mimic malignancy 2
• CA 19-9 and CEA as tumor markers, though CA 19-9 can be falsely elevated in biliary obstruction (note: one case report showed pembrolizumab-induced pancreatitis with elevated pancreatic tumor markers that normalized with steroid treatment) 4
• Stool ova and parasites for liver flukes (Clonorchis, Opisthorchis) given Philippines exposure 2

Urgent Interventions:

• Empiric broad-spectrum antibiotics (piperacillin-tazobactam 3.375g IV q6h or ceftriaxone 2g IV daily plus metronidazole 500mg IV q8h) should be started immediately if any signs of cholangitis (fever, rigors, altered mental status) pending culture results 2
• Vitamin K 10mg IV daily × 3 days for INR 1.47 to correct coagulopathy before ERCP 2
• Aggressive IV hydration with lactated Ringer's to maintain urine output >0.5 mL/kg/hr given risk of hepatorenal syndrome with severe cholestasis 2
• Hold pemetrexed until biliary obstruction resolved and liver function improves, as hepatic dysfunction significantly increases pemetrexed toxicity 5, 6

Oncologic Assessment and Systemic Therapy Considerations

Current Cancer Status:

• Pemetrexed continuation should be reassessed after biliary decompression—the patient is on appropriate maintenance therapy for nonsquamous NSCLC, and outcomes data show median overall survival of 20.3 months with pembrolizumab-pemetrexed maintenance versus 12.0 months without pemetrexed 7
• Restaging imaging with contrast-enhanced CT chest/abdomen/pelvis after biliary decompression to assess for new metastatic disease, particularly periportal/celiac lymphadenopathy that could explain biliary obstruction 1
• Molecular testing if not previously done—check for MSI-H/dMMR status, as pembrolizumab monotherapy achieves 34.3% overall response rate in MSI-H tumors across cancer types, though the patient's prior pembrolizumab-induced pancreatitis complicates rechallenge 3, 8

Pembrolizumab Rechallenge Considerations:

Do not rechallenge with pembrolizumab given prior grade 3-4 drug-induced pancreatitis, as immune-related adverse events have high recurrence rates (up to 74% experience adverse events, with 20% grade 3-4) and can be life-threatening 3. The current peripancreatic fluid collections may represent chronic changes from prior pembrolizumab pancreatitis rather than active disease 4.

Definitive Management Plan Based on ERCP Findings

If Malignant Obstruction Confirmed:

• Biliary stenting (metal stent preferred for longer patency in malignant obstruction) with plan for repeat ERCP every 3-4 months or as clinically indicated 2
• Continue pemetrexed maintenance once bilirubin <3× ULN and transaminases improving, as pemetrexed remains effective in nonsquamous NSCLC with favorable toxicity profile 5, 6, 7
• Consider palliative radiation to porta hepatis if bulky lymphadenopathy identified as cause of obstruction 1
• Early palliative care referral at this juncture rather than waiting for end-stage disease, focusing on quality of life and symptom management 1

If Infectious/Inflammatory Etiology:

• Targeted antimicrobial therapy based on culture results and sensitivities 2
• Corticosteroids (prednisolone 1 mg/kg/day) if IgG4-related disease confirmed or if recurrent immune-related pancreatitis suspected, with gradual taper over 2-3 months 4
• Resume pemetrexed once infection cleared and liver function normalized 7

Critical Monitoring Parameters

• Daily bilirubin, alkaline phosphatase, transaminases until downtrending after biliary decompression 2
• Coagulation panel every 2-3 days until INR <1.3 2
• Renal function daily given risk of hepatorenal syndrome and need for contrast procedures 2
• Lipase every 2-3 days to monitor for worsening pancreatitis 4
• Clinical signs of cholangitis (fever, mental status changes, hemodynamic instability) requiring urgent repeat ERCP if stent occlusion suspected 2

Prognostic Considerations

The presence of biliary obstruction from metastatic disease significantly worsens prognosis, with median survival typically 4-6 months without effective systemic therapy 1. However, if biliary decompression is successful and pemetrexed can be continued, median overall survival of 12-20 months remains achievable based on maintenance therapy data 7. Venous thromboembolism prophylaxis with enoxaparin 40mg SC daily is essential, as pancreatic/biliary malignancies have the highest VTE rates among all cancers, and VTE is the second leading cause of death after the cancer itself 1.

Common Pitfalls to Avoid

• Delaying ERCP for additional imaging—proceed directly to ERCP for combined diagnosis and therapy 2
• Administering pemetrexed with severe hepatic dysfunction—hold until bilirubin <3× ULN to avoid life-threatening toxicity 5, 6
• Rechallenging with pembrolizumab after grade 3-4 immune-related adverse event—contraindicated due to high recurrence risk 3, 4
• Attributing all findings to malignancy without excluding treatable infectious causes given recent travel 2
• Inadequate vitamin K replacement before invasive procedures with elevated INR 2