Biliary cancer, with around 5500 new cases per year, is one of the rare forms of cancer, but it is particularly risky. According to popular opinion, the tumor causes almost no early symptoms and is therefore usually only recognized late when an operation is no longer possible and the tumor has already metastasized.

Biliary cancer – important: inside or outside the liver

The fact is, however, that the colloquial term biliary cancer, medically cholangiocarcinoma (CCA), covers different forms. First of all, there is gallbladder cancer, which forms in the gallbladder, which in turn is embedded in the liver.

Secondly, a carcinoma can form in the bile ducts, which are not only located within the liver and direct the bile to storage in the gallbladder, but also away from the gallbladder, which lead the bile to the small intestine.

“Depending on the localization, we differentiate between intra- and extrahepatic carcinoma, i.e. those that develop inside or outside the liver,” explains Arndt Vogel, spokesman for the “Hepatobiliary Tumors” working group of the Internal Oncology Working Group (AIO) and head of the Visceral Oncological Center Hannover Medical School (MHH).

The risk of developing cholangiocarcinoma increases with age. Overall, the incidence of intrahepatic carcinomas is increasing, while that of extrahepatic carcinomas falls somewhat.

Risk factors for biliary cancer

An exception in connection with cholangiocarcinoma is Southeast Asia, especially countries like Thailand. This cancer often occurs there because certain parasites can inflame the biliary tract. Chronic inflammation plays an important role in the development of biliary cancer.

The following risk factors come into play in the western industrialized nations, but they are also closely related to inflammation:

• Primary sclerosing cholangitis, an inflammation of the bile ducts that mostly affects men.
• Cysts in the bile and bile ducts, including Caroli’s syndrome; they increase the risk of biliary cancer.
• Smoking, because the substances in smoke are known to be carcinogenic, are not only excreted via the kidneys and urine, but are also collected, processed and passed on in the bile.
• Gallstones; However, only when they cause problems, i.e. inflame the bile, do they promote the development of cancer.

Gallstones and biliary cancer

Around ten percent of Germans are said to have gallstones, and the risk increases with age. “But very few of those affected develop cholangiocarcinoma. This cancer is very rare, ”says the medicine professor reassuringly.

The gallbladder should only be removed if the stones cause problems, i.e. colic and inflammation.

Symptoms appear differently late, but are similar

The signs of gallbladder inflammation caused by stones are somewhat similar to those of cholangiocarcinoma (CCA).

So biliary cancer can cause the following signs:

• Jaundice (jaundice)
• nausea
• Vomit
• Pain in the left upper abdomen.

The location of the carcinoma is crucial for the stage at which symptoms appear:

• Intrahepatic carcinoma triggers these clear signs quite late, “because the liver doesn’t hurt when a tumor grows there,” explains the expert.
• Extrahepatic carcinoma, on the other hand, usually quickly means that the bile can no longer flow into the intestine. Bile congestion and jaundice are relatively early signs of this type of cancer.

That is why bile duct cancer that grows outside the liver is usually diagnosed earlier – but it is difficult to operate because of its often complicated location next to blood vessels and does not make the generally difficult situation with cholangiocarcinoma any easier, the oncologist limits the associated high expectations.

Diagnosis of cancer of the gallbladder and bile ducts

Doctors use cross-sectional image diagnostics such as MRI and CT. “This allows the suspicion to be clarified and the staging, i.e. stage and spread, to be identified,” explains Vogel.

The histological examination provides additional details about the tumor, whereby the samples in gallbladder cancer are relatively easy to obtain. However, this is more difficult with extrahepatic tumors because the biliary tract is often narrow and winding. The examination is carried out through an endoscope, the method here is called endoscopic retrograde cholangiopancreatography (ERCP examination).

Are there any less invasive methods? Ultrasound, carried out endoscopically through the stomach from the inside or from the outside, can also be informative, says the cancer specialist. However, the methods of first choice are MRI and CT.

Treatment of biliary cancer – surgery not always possible

If the suspicion has been confirmed and the results of the examination enable the tumor to be classified, the goal is to remove the carcinoma surgically. “However, as already described, this is sometimes difficult due to the location of the tumors,” reports Vogel. However, the surgical techniques have improved significantly in recent years.

The standard treatment for patients with advanced tumors is chemotherapy, with a combination of gemcitabine and cisplatin.

In a palliative situation, i.e. to lengthen survival time and / or improve quality of life, local therapies such as selective internal radiotherapy (SIRT, radioembolization) are currently used in clinical studies . Radioactive microspheres are guided to the tumor via an inguinal catheter, its cells are destroyed and healthy tissue is spared. The first results show that for some patients many months can be gained with this.

The prognosis for biliary cancer is poor …

Despite all these possibilities, few patients can be cured. Even if the tumor could be completely removed in the healthy, the recurrence rate is still relatively high. “60 to 80 percent of the tumors come back,” reports Vogel. Because the tumors spread very early.

… but with the therapy “a small revolution is emerging”

This is the bad news. In fact, these prospects could improve in the future. The oncologist says: “Because a small revolution is taking place here at the moment.” The interest of pharmaceutical companies in this rare cancer has increased significantly, and intensive work is being carried out on the development of new drugs.

The reason for this change is the fact that it has been discovered that numerous genetic changes occur in these tumors and thus allow a molecular, i.e. targeted therapy. There have been many studies on this topic for a few years now.

Two developments are particularly promising:

1. Inhibitors against IDH1 mutations , from which patients with a corresponding cholangiocarcinoma can clearly benefit.

2. Inhibitors against FGFR2 , fusions, MSI, NTRK and others.

“There are currently a number of very promising active ingredients in the test that have the various genetic changes as a starting point,” reports the oncologist. How much these new therapies could improve the treatment of biliary cancer becomes clear when one realizes that 40 to 50 percent of all these tumors, especially intrahepatic ones, show such genetic changes and are therefore suitable for targeted, molecular therapy.

Prevention Of Bile Cancer – Quit Smoking!

However, it will be some time before the new therapies are available to all patients. Until then, it is still true that biliary cancer is difficult to treat and the prognosis is unfavorable.

This makes prevention all the more important. To what extent can everyone prevent this tumor – apart from the advice not to smoke, which is so important with regard to many other diseases? The expert also has one recommendation in particular:

Get gallstones cleared up if they’re causing problems. However, this does not mean that everyone who has gallstones should be afraid: Gallstones are considered to be risk factors for gallbladder cancer, but only one percent of all gallstone carriers develop this tumor.

• The body’s own stem cells have a positive effect on osteoarthritis-related inflammation in the knee.
• A study now wants to clarify whether they actually build up permanent cartilage.
• A transplant can repair minor cartilage damage in young patients.

After a certain age, signs of wear and tear become noticeable in the knee . After the age of 30, the risk increases linearly. The painful, inflammatory breakdown of cartilage in the operating room and with an artificial knee ends 150,000 times a year. Then smooth metal has to replace the cartilage layer, which allows round, painless movements in a healthy knee.

The idea frightens many people suffering from osteoarthritis. They hope for new methods to rebuild lost cartilage: stem cells should help.

Belly fat provides the best stem cell material

The doctor uses the patient’s belly fat as a starting material. The idea behind it: stem cells can be obtained particularly easily and in relatively large numbers from vascular fat tissue. Injected at the location of the defect, they learn from the microenvironment into which cell type they should develop.

According to this principle, the doctor and stem cell researcher Eckhard Alt uses the undifferentiated cells : Stem cells from the patient’s fat tissue are processed in the operating room within an hour and injected into the patient where he needs them – for example into the osteoarthritis knee.

The founder of the “Interdisciplinary Stem Cells Research Center” in Houston and a private clinic in Munich sees stem cells as the future therapy for chronic inflammatory diseases of the musculoskeletal system – among other things.

The cell extract in the knee does not guarantee success

Some orthopedic practices that offer the procedure honestly state that it is a not generally recognized attempt at healing with no guarantee of success. Rather, it is a final experimental attempt to remedy knee problems without a joint replacement.

“In this so-called ‘point-of-care’ application, a cell extract is injected that not only consists of stem cells,” explains Oliver Pullig from the Fraunhofer Translational Center for Regenerative Medicine in Würzburg. How many stem cells that are supposed to develop into cartilage material actually get into the knee is just as little regulated as the preparation of the suctioned off belly fat.

Stem cells instead of knee prostheses

A Europe-wide study is currently looking for scientific evidence of the anti-osteoarthritis potential of the body’s own stem cells.

A small one with six patients in Würzburg and twelve in Montpellier, France, led to success in 2013: Almost all participants canceled their previously unavoidable operation for a knee prosthesis. “Your complaints had improved throughout,” explains Oliver Pullig. “A reconstruction of cartilage was unlikely with such a large damage.”

The follow-up study that has just begun with 153 participants at ten European locations therefore fulfills a requirement that the German study director Ulrich Nöth from the Evangelical Forest Hospital Berlin-Spandau formulated back then: Stem cell therapy is best suited for patients with middle and middle-aged osteoarthritis. You are no longer eligible for a cartilage transplant, but you are too young to have an artificial joint.

New cartilage from stem cells? A study should show it

Like the pilot study, the ADIPOA2 study uses so-called mesenchymal stem cells from the abdominal fat of each subject. These precursor cells of the connective tissue have the ability to develop into cartilage, bone or fat cells.

Biologist Oliver Pullig explains: “We take 100 milliliters of belly fat from each participant. The stem cells obtained from this are multiplied millions of times in special laboratories. That takes a good two weeks. 51 patients then receive two million of these pure stem cells injected into the joint, 51 patients receive an injection with 10 million cells and 51 patients receive a placebo. “

Results should be available by the end of 2018, and thus scientific proof of whether stem cells fulfill the hope of permanently building cartilage. The scientist is optimistic: “If successful, the therapy with stem cells as a drug could be ready for the market at the next study level. It doesn’t take five years. “

Cartilage transplant only helps to a limited extent

Another method to restore lost cartilage is transplantation, which has been tried and tested for 20 years. So far, however, it has only been successful in the case of centimeter damage in an otherwise intact knee. The operation is laborious and the healing process long.

In the first keyhole surgery, the doctor removes a small piece of healthy cartilage, hardly larger than a grain of rice. These cartilage cells are propagated in the laboratory in three to four weeks. In a second operation, the surgeon places these cells or the cartilage patch on the defective area in the knee.

After that, the knee must not be subjected to any load for six weeks, then only lightly for another six weeks. Only after a year is the joint stable enough for sport to be possible.

Cartilage from the laboratory is expensive

The transplant is only suitable for younger knee patients whose cartilage and joints are free from osteoarthritis. If this therapy is successful, it can prevent further cartilage damage and a later threatened knee prosthesis.

Then, in the long term, the costs of several thousand euros for cells grown in a laboratory will pay off.

Hyaluronic acid can at least relieve pain

If these methods are out of the question, another remedy can help: synthetic hyaluronic acid is often misunderstood as a substance for building up cartilage. However, it cannot produce worn cartilage, but serves as a lubricant and for joint care.

Orthopedic surgeons inject the moisture-retaining gel three to five times at weekly intervals. Hyaluronic acid relieves pain and promotes mobility – permanently for some patients, at least for a year or two for others. Then the treatment can be repeated.