Question 1

You mentioned recurrence rates even after surgery. Can you expand on that?

Dr. Ashish George · Accepted Answer

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.

Question 2

The majority of HCC patients present late, with very large lesions up to 10 centimetres, and liver transplant isn't available in most of our countries. What criteria should guide resection in that setting?

Dr. Ashish George · Accepted Answer

The first check is whether the background liver is cirrhotic. Some patients with vertically transmitted hepatitis B or C are carriers with an essentially normal background liver; there, extended resections are possible, using portal vein embolisation of the involved side to enlarge the future liver remnant. On a cirrhotic background, every effort goes into ruling out extrahepatic disease, then grading any portal vein invasion from VP1 (a segmental branch) through VP2 (a sectoral branch) and VP3 (the right or left main branch) to VP4 (the main portal vein). Patients with a large primary and VP1 or VP2 involvement, and no extrahepatic disease, can still be offered liver transplant, upfront or after downstaging: TACE for the primary, sometimes over one to three sessions for large tumours, and SBRT for the tumour thrombus, or even for a very large primary where TACE is not advisable. The aim is stable disease over 12 weeks, with no extrahepatic disease, a significant fall in tumour markers and no progression within the liver; patients who achieve this can be offered transplant.

Question 3

We see many non-cirrhotic HCCs, mainly from hepatitis B, and a good number are resectable at 2 centimetres, but we struggle to get these patients optimised for surgery. How do you approach them?

Dr. Ashish George · Accepted Answer

We are extremely aggressive when we get a non-cirrhotic liver. In our practice these are not common: of 100 HCCs, perhaps 95 arise on a background of cirrhosis and only 5 on a non-cirrhotic liver. For those 5 patients we will do extended resections, use portal vein embolisation, and even ALPPS, a staged hepatectomy, is an option. If the liver is normal, even removing almost 80 percent of it leaves a remaining 20 percent that should grow back and take care of all liver functions, which is why resection is pursued much more aggressively in these patients.

Question 4

How do you make a diagnosis of HCC, and is liver biopsy common?

Dr. Ashish George · Accepted Answer

HCC has a characteristic imaging signature, so biopsy is reserved for genuine diagnostic dilemmas. In a cirrhotic liver, 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, and a lesion in a non-cirrhotic liver needs a biopsy. Around 40 percent of HCC patients have an elevated AFP, meaning 60 percent do not, so diagnosis relies on radiology rather than tumour markers.

Question 5

In cholangiocarcinoma, is there a bilirubin cut-off above which you would not operate?

Dr. Ashish George · Accepted Answer

No. We have operated on patients with a bilirubin of 30 to 35; this applies to hilar cholangiocarcinoma, since intrahepatic tumours usually do not present with jaundice and are usually unresectable by the time they involve the hilum. Five to ten years ago, extended resections in perihilar cholangiocarcinoma would leave only the left lateral section or the right posterior sector. Now we can sometimes do a left or right resection with the caudate and an extended bile duct resection to preserve more liver parenchyma. Unless the patient has cholangitis, we may resect even without preoperative biliary drainage. Drainage of the future liver remnant is done for patients with cholangitis or those planned for upfront portal vein embolisation before an extended resection, either by PTBD or by nasobiliary drainage (ENBD); in our setup it is mostly PTBD.

Question 6

Between CA19-9 and alpha-fetoprotein, which is more specific?

Dr. Ashish George · Accepted Answer

Alpha-fetoprotein is the tumour marker primarily elevated in hepatocellular carcinoma. CA19-9 comes primarily from the biliary system; it may be elevated in patients with cirrhosis, but the level of elevation is not very high.

Question 7

After surgery, does the patient take any anti-cancer drugs, and if so, which ones?

Dr. Ashish George · Accepted Answer

For hepatocellular carcinoma treated by resection, we would place these patients on lenvatinib, most of the time for a long period. After transplant there is usually no separate adjuvant drug treatment; instead the standard immunosuppression is modified. Everolimus, an immunosuppressive drug, is associated with a lower risk of recurrence after liver transplant for HCC, so instead of the standard tacrolimus and mycophenolate we use tacrolimus plus everolimus. In cholangiocarcinoma with lymph node or vascular invasion, patients are referred to the medical oncologist, who decides fitness for adjuvant chemotherapy. Many of these patients are run down after preoperative jaundice and recurrent cholangitis; once they recover, perhaps after 6 to 12 weeks, adjuvant therapy can be offered: capecitabine, as on the slides, or a cisplatin or gemcitabine-based regimen.

Question 8

A patient developed deranged bilirubin and liver enzymes after a Pringle manoeuvre during hepatectomy, was managed conservatively and then stented at ERCP. Is this a common complication of the Pringle manoeuvre?

Dr. Ashish George · Accepted Answer

No, this is not a common complication. Needing a stent means the bile duct is involved. After a right hepatectomy for an intrahepatic cholangiocarcinoma, for example, an accidentally narrowed biliary confluence can cause jaundice. After a hepaticojejunostomy for hilar cholangiocarcinoma, a bile leak that later becomes a stricture can cause postoperative jaundice needing stenting. The only other setting is preoperative radiotherapy, where the vascularity of the bile duct is in question and an anastomosis may stricture. Otherwise, the Pringle manoeuvre may raise liver enzymes, but jaundice from biliary obstruction should not happen.

Question 9

What is the guidance on follow-up for HCC and cholangiocarcinoma to prevent recurrence?

Dr. Ashish George · Accepted Answer

For hepatocellular carcinoma treated by resection or by an interventional procedure such as microwave ablation, TACE or radiofrequency ablation, the background liver still carries a risk of new cancers, so strict follow-up is needed. Resected patients need more detailed imaging than ultrasound alone. CT can be used, but it carries radiation and a risk of contrast nephropathy, so MRI is used more often; the goal is to pick up smaller lesions earlier, while they can still be resected or treated with salvage transplant. For cholangiocarcinoma, CT or MRI is again preferred over ultrasound, which may not detect lesions early enough. Tumour markers are also followed: alpha-fetoprotein and PIVKA-II for HCC, and CA19-9 for cholangiocarcinoma.

Question 10

What does it take to have a transplant-capable centre?

Dr. Ashish George · Accepted Answer

First is intent. Even in India, only a few government centres perform transplants; the push has come primarily from the private sector, because governments face more pressing issues that require less infrastructure and cost. Transplant demands substantial infrastructure: a very good interventional radiologist, good CT and MRI with phasic scans, and an apheresis machine for ABO-incompatible transplants. Second is mentorship: people already trained in transplant need to help with the first cases so that the skill set transfers. In our experience the programme was primarily surgeon-driven, and radiology, anaesthesia, critical care and hepatology sometimes became the constraints, so every discipline must be equally dedicated. Management must be completely behind the team, because transplant takes far more time and effort than routine GI or hepatobiliary surgery. Today mortality in liver transplant is an exception: across the board, perhaps 5 or 7 of 100 transplant patients die, and the majority go home walking. That is why a new programme should work with experienced teams so the skill transfer happens without patients suffering.

Question 11

A 60-year-old woman presented with right upper quadrant pain for three months. Investigations suggested a hydatid cyst, but the CT suggested a pericytoma, and after two months the lesion has not improved significantly. How should it be managed?

Dr. Ashish George · Accepted Answer

Please share the scan itself, not the films (the CD uploaded to Google Drive), so I can review it and we can discuss the diagnosis and treatment for this patient. In general, if it is a resectable tumour of 3 to 3.5 centimetres, you can go in and resect it upfront with a margin and wait for histology; you do not need to make the diagnosis beforehand. If a hydatid cyst is still in the differential, though, give albendazole cover beforehand and protect the operative field against spillage. With a tumour that small, loss of liver parenchyma or derangement of liver function should not be an issue. Remove it, send it for histopathology, and you will have your answer.

Live Discussion with Dr. Ashish George