Adjuvant and Systemic Therapy, and the R1 Resection Question, in Cholangiocarcinoma

Hepatocellular carcinomas develop on a cirrhotic liver, which is like a fertile field: removing one tumour by resection or ablation does not remove the underlying tendency of that liver to produce another. Because the diseased liver stays in place after resection or ablation, these patients carry a higher ongoing risk of new tumours. A transplant removes the whole diseased liver and replaces it with one that does not carry that risk, which is why upfront transplant can be the better option even when a tumour looks resectable.

The first check is whether the background liver is cirrhotic or, from vertical hepatitis B or C transmission, essentially normal; a normal liver allows extended resection with portal vein embolisation to grow the future remnant. On a cirrhotic background, the priority is ruling out disease outside the liver, then grading any portal vein invasion from VP1 (a segmental branch) to VP4 (the main portal vein). Patients with VP1 or VP2 involvement and no extrahepatic disease can still be offered transplant, upfront or after downstaging with TACE, sometimes combined with SBRT for a portal vein tumour thrombus, aiming for 12 weeks of stable disease.

Non-cirrhotic HCC is uncommon in Dr. George's own caseload, around 5 patients in every 100 he sees, but for exactly this group his unit is far more aggressive: extended resections, portal vein embolisation, and even ALPPS, a staged hepatectomy, are all options, because a normal liver can lose as much as 80 percent of its volume and still regenerate enough function from what remains.

HCC has a characteristic imaging signature, so biopsy is reserved for genuine diagnostic dilemmas. An arterially enhancing lesion with venous washout on a properly phased triphasic CT is treated as diagnostic in around 95 percent of cases; MRI is used when the CT is inconclusive. Around 40 percent of HCC patients have an elevated AFP, meaning 60 percent do not, so diagnosis relies on radiology rather than tumour markers.

No. Dr. George has operated on perihilar cholangiocarcinoma patients with bilirubin as high as 30 to 35. Surgical practice has also evolved: where extended resections once left only the left lateral section or right posterior sector achievable, his unit now more often does a left- or right-with-caudate resection with extended bile duct resection, preserving more liver parenchyma. Preoperative biliary drainage, usually percutaneous (PTBD) rather than endoscopic nasobiliary drainage, is reserved for patients with cholangitis or those planned for portal vein embolisation.

Most perihilar cholangiocarcinoma patients do not ultimately die of liver failure, they die of cholangitis and sepsis. Removing the tumour, even with a histologically positive margin, combined with biliary drainage, addresses that risk and produces meaningfully better outcomes than no surgery at all.

Capecitabine is used in the adjuvant setting and is associated with improved survival. Gemcitabine and capecitabine together are used in the neoadjuvant setting to downstage tumours before an attempted resection.

Gemcitabine plus cisplatin is the first-line systemic treatment for advanced, inoperable intrahepatic cholangiocarcinoma. Immunotherapy and targeted therapies have also been used in some studies.

Patients often arrive debilitated from preoperative jaundice and recurrent cholangitis, and typically need six to twelve weeks to recover before adjuvant cisplatin or gemcitabine-based treatment can begin.