Surgery and Liver Transplant at MDA
The following remarks were transcribed at the Worldwide NET Cancer Awareness Day Patient Education Event sponsored by Caring For Carcinoid Foundation www.caringforcarcinoid.org
FOCUS ON MID-GUT CARCINOID SURGERY
Jason Fleming, Assoc. Prof. Surgical Oncology – This is an area of confusion from a surgeon's standpoint. Most of us realize certain sized tumors should be removed. But we still have a lot of work to do in the US because we lack standardization in this area.
SOME BASIC CONSIDERATIONS
The way we look at carcinoid surgery is the way we should look at any cancer surgery:
- Understand the biology of tumor you are removing.
- Detailed knowledge of the pertinent anatomy
- Goals of operation – what are you trying to achieve with surgery?
CASE HISTORY: A 63 year-old man had an ulcerated mass in ileocecal valve identified during routine colonosocopy. A biopsy identified a well-differentiated neuroendocrine tumor. He was taken to the operating room for a planned resection.
OPERATIVE REPORT – A large nodal primary was found with metastasis to lymph nodes and multiple liver lesions. The surgeon took the right colon, and several lymph nodes but there was also a mesenteric artery mass. Generally we're told in the US to avoid anything near the artery. So the surgeon took the primary tumor out and left the lymph nodes in. We generally see that in consult here.
According to the SEER data - of 3,500 patients,1500 of them had the small bowel removed; 221 had no lymph nodes removed – just tumor. 1100 had at least one lymph node removed. So the large majority of carcinoid surgeons are getting the primary tumor out only. They operate on the problem they are there for and nothing more.
This is general surgical practice that affects the outcome for patients in the US. The question is: Do you take out the mesentery met?
There are many factors to consider. You must determine whether it's low grade or whatever. When you see it's low grade, you may think it is the good kind. But what you see on initial biopsy is not necessarily what you see over time. The nodes may look completely different from the primary.
We know the primary tumor becomes more aggressive. NETs can fool even clinicians into thinking they are dealing with something slow.
THE GENETIC DIFFERENCES OF CARCIOID
Looking at the DNA, the more lines you see, the more genetic abnormalities there are. Comparing ileal vs other NETs, genetics show they may not even look like the same cancers.
If you look at the histology of well-differentiated tumors, most patients are going to do pretty well from histology viewpoint. A NETs patient presenting with liver mets could survive years. The patient presenting adenocarcinoma with mets is more likely to have survival of months.
There is a thought that, "Oh the patient has liver mets. He's a gonner. No need to take out." But with NETs the surgeon needs to get regional control because these NETs patients with liver mets can live years.
Lymph node mets are more likely and more dangerous than you think.
You can track lymphatic drainage. We inject dye where a tumor is and track where lymph drains to.
We find that most lymph node trails are like a series of filters. So metastasis is not random, it follows an anatomic and physiological path. So you know which lymph nodes will be likely to develop metastasis. The first echelon is adjacent to the tumor then more and more distant.
Proximal to Distal Approach
In Sweden, there was an article about dividing blood vessels to take tumors in the lining out. So you can take tumor out and actually save the bowel. That might affect the goal of your operation. Metastatic lymph nodes can can grow and obstruct these veins and get small bowel so it can't function and the patient will die. So patients who elect to have these lymph nodes taken out survive longer. Even removing lymph nodes without doing anything for the liver helps the patient do better.
If you remove more or less than eight lymph nodes, it results in improved survival. Detailed knowledge of anatomy determines whether the benefit outweighs risk and we recommend it.
Side effects of cancer surgery
Many of the problems are usually from rapid transit, Bile salts no longer are reabsorbed in the ileum. The bile salts get dumped into the colon and the colon doesn’t like that and causes diarrhea.
Also (the effects of) hormonal excretions can look like short gut syndrome. Use cholestyromine to bind bile salts. Steatorrhea (floaties) usually come from pancreatic involvement. When the pancreas is not active enough, you get rapid transit. Take pancreatic enzymes.
NETs patients rarely get pellagra, these days.
Q: Have you dealt with any cases of mid-gut that were not operable?
Lymph nodes can actually start to pull in surrounding tissue and begin to restrict blood flow to intestine. An experienced surgeon can tell if that's happening.
Q: Why do so many of our tumors not show on MRI or CT?
There's very high variability in the quality and interpretation of images in US. Techniques differ in how contrast is given. There can be subtle but important differences in that. It can mean the difference between seeing and not seeing tumor. So, I recommend re-imaging in four months.
Q:What if a patient wants a second opinion?
I encourage second opinions. Surgeons who are confident will say, “I would love for you to get a second opinion. In fact, here are some people in your area of the country who you might contact.”
Q: Can you have mets in the liver before having tumors in the lymph nodes or elsewhere?
The lymph system is a parallel system to the blood system. Tumor cells detach from the primary and travel, either through blood or lymph. Nodes are supposed to trap mets but blood travels directly to the portal vein and into liver.
FOCUS ON LIVER SURGERY
Thomas Aloia, Assist. Prof. Medical Oncology
Identified himself as a "recovering transplant surgeon."
"In some cases tumor cells travel through the blood stream. NETs is an incredibly complex disease. You have to take into account a lot of factors. You can’t always predict a tumor's biology. Some tumors have no hormone production. Others may be tiny and cause profound symptoms.
Q: If you are going to operate on liver and there is disease outside liver how to deal with that?
Depends if it is an aggressive type (of NETs) – poorly differentiated, Ki-67 positive, with early recurrence after resection is not a good candidate for surgery.
If the disease is classified moderate, these patients benefit most. Tumor growth causes injury to the liver. It may produce hormones that are debilitating.
If the classification is indolent – slow - maybe no hormones are being produced and no surgery is needed. Slow-growing cases often have good immune systems that keep growth down, so if you do transplant, you also ablate the immune system. So that's not so not good.
Liver resection
You can cut out one side of liver and allow other side to regrow in 6 week or a few months.
In surgical terminology:
R0 (R-zero)- resection – means 100% removal of tumors or cancerous tissue.
R1 – resection – 90%+ removal. It can benefit some patients – even if not all tissue gone. Symptom control is a benefit. Their mortality rate low - less than 1%. Most survive 5 years. Patient selection is important. You might not attempt a patient with bulky disease.
As of 2006 I saw 1,000 patients.50% had tumors in the small gut.
76% survive 5 years and certainly some patients did recur but they are alive with disease. We think selection of patients and the technical ability of the surgeon is an advantage.
Nuance is crucial to treatment sequencing. We have to pick what we will do and get the sequence correct. Without dialog in the treatment team, we can’t expect that to happen.
We are careful to address the symptomatic disease. We want to improve quality of life. Also the patient may be nearing increased symptoms and we may be able to intervene early.
Q: What about liver transplant for NETs?
Ki-67 level is important – lower is better. International criteria have been proposed. Those likely to be selected are:
- Patients in whom 50% of the liver is replaced by hepatic tumor, they have no outside tumor, they have confimed carcinoid histology, their primary was drained by the portal vein.
- We can do a transplant with less factors. It depends.
Minimally invasive liver surgery has been developed. We can make a two-inch incision on the belly, a camera is inserted, also light and a tool to heat, cut and seal the liver resection. We irrigate, place a clip on the large vessel through ¼ inch incision. The we move around and locate the tumor with EUS (ultrasound,) insert a plastic bag in abdomen and put the tumor specimen in the bag, then take out bag so we don’t spread tumor cells. Compared to the foot-long liver surgery, there's less pain and early return to normal activity,
Personalized medicine
More and more the multidisciplinary approach to NETs is trying to discern the unique characteristics of each patient and evaluate risk factors and advantages We want to determine the trajectory to get which treatment is best. This is best done in multi-disciplinary setting.
MDA does not do liver transplants but nearby facilities do and when appropriate, we can refer patients to them.
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How to decide between RFA or Nanoknife?
It's best to involve a surgeon. Your first goal should be done for the removal of tumors. You want to have confirmation that cancer cells that the are out of the body. If you use NanoKnife or RFA and tumor is left in the body you are more likely to see recurrence after resection. But at times, when the structure of the liver doesn’t allow open surgery, you have to consider one of these other, less invasive approaches.
Liver surgery has become incredibly safe procedure procedure.
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