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 latest news from German slaughterhouses have certainly given the vegetarians and vegans community a new boost. In addition to animal welfare and ecological aspects, avoiding meat is usually also based on the desire for a healthy diet. What does science say

1. Consensus: little meat is okay, but not really necessary

Every German eats 150 grams of meat and meat products on average every day. That doesn’t sound like a lot, but it clearly exceeds the maximum 600 grams that the German Nutrition Society per week finds acceptable. Many consumers are also significantly higher. It is these “meat eaters” who are mentioned in the studies on the harmful effects of meat consumption.

But even with those who eat a lot of meat, there are differences: because those who eat a lot of unprocessed meat, and at the same time high in fiber and low in sugar, have a low risk of disease. This is the case, for example, with the Paleo diet.

Experts consider the Mediterranean diet to be the best nutritional method in the world, and it has been for two decades. In 2019 she was once again named the best diet of the year by “US News” . A lot of vegetables, fish and olive oil end up on the plate, but little meat and processed foods.

In comparative studies, it is not vegetarians and vegans who do well, but people who eat little meat.

But you can also say with a clear conscience to Tilmann Kühn, nutritional epidemiologist at the German Cancer Research Center (DKFZ) in Heidelberg: “If you eat wholesome vegetarian food, your body is fine. On the contrary, according to scientific findings, a vegetarian diet is actually very healthy. ”With one small caveat:“ Less meat ”only makes sense if the calorie advantage is not topped up with pizza, biscuits or meat imitations.

2. Those who do not eat meat also live more healthily in other ways

Numerous studies have shown that the biggest meat fans usually do not have good eating habits. Even if you neglect the nutritional value of individual foods, a diet high in meat and sausage as well as sugar, white flour and saturated fats from ready-made foods is unhealthy. Because healthy foods such as vegetables, fruit, legumes, whole grains or nuts are definitely neglected.

3. meat or plant? Nutritional studies are conditionally meaningful

In the laboratory, it is possible to determine how certain nutrients affect human cells. Studies with humans don’t work like that. The health comparison “meat eaters versus vegetarians” is only possible in observational studies. Their conclusions are only an approximation of reality. Too many factors play a role in health for the question to be reduced to schnitzel and tofu . For example: is a chain-smoking vegan healthier than an athletic meat eater?

Epidemiological studies can never conclusively prove that meat consumption is unhealthy. And it is also not conclusively clear which individual ingredients are harmful to health.

4. When it comes to meat, it depends on the color

Beef, pork, lamb or sheep provide the so-called red meat. It is said to cause cardiovascular diseases and problems with the blood vessels.

For US researcher Stanley Hazen from the Cleveland Clinic, a metabolic product of the carnitine contained in red meat is responsible for this. To prove this, he had 113 test subjects eat 250 grams of steak a day for four weeks. A two-week break was followed by four weeks with a correspondingly large amount of (white) poultry meat and, at the end, a meat-free month.

The result , published in the “European Heart Journal”, showed a significant 3-fold increase in the TMAO plasma concentration during the steak weeks. TMAO is produced during the metabolism of carnitine and is a risk marker for hardening of the arteries in the blood vessels. The diet with poultry and vegetables led to a decrease in plasma concentrations in the test subjects.

Red meat is also directly or indirectly involved in the development of cancer.

For example, studies by the DKFZ have shown that people who eat a lot of red meat have increased biomarkers of certain roasting substances, such as those produced during roasting and grilling, swim in the blood. These people were at an increased risk of developing colon cancer.

In the large-scale EPIC study across Europe, 519,000 test persons were examined to find out the connection between diet and cancer .

The results show that red meat can increase the risk of colon cancer. Accordingly, the risk of the disease increases by almost 50 percent if the daily consumption of meat is 100 grams above the recommended amount. The same amount of sausage products increases the risk by as much as 70 percent.

The risk of stomach cancer is also said to be related to heavy meat consumption. In people infected with the Helicobacter pylori bacterium, the risk increases by a factor of five.

5. Theory 1: Iron makes meat unhealthy

There are various theories about why red meat is so problematic. The so-called iron load hypothesis is based on the fact that red meat contains a comparatively high amount of iron. This so-called heme iron has a high bioavailability, unlike iron from plant food, and thus enters the organism in larger quantities.

It has long been suggested that high levels of iron in the blood increase the risk of cancer . However, this theory has not yet been proven by studies.

6. Theory 2: BMMF make meat unhealthy

Scientists working with Nobel laureate Harald zur Hausen believe they have found another cause: a previously unknown class of pathogens is responsible for the increased risk of colon cancer .

These “Bovine Milk and Meat Factors (BMMF)” enter the human intestines through the consumption of meat and dairy products from European cattle. There it comes to a chronic inflammation, which indirectly promotes the development of colon cancer.

7. Avoiding meat protects the intestines

Vegetarian foods contain fiber, which has a positive effect on the microbiome in the gut. Vegans have a particularly large number of them. In addition to fruit and vegetables, lactic acid foods such as yogurt also support the intestinal flora. Vegetarians often consume these. Researchers from the University of New York have confirmed that vegans and vegetarians have more protective types of gut bacteria than meat eaters.

Meat also poses a cancer risk through its preparation and processing: for example, when meat is heated up, several potentially harmful substances are formed at the same time, including so-called polycyclic aromatic hydrocarbons (PAHs); curing also produces nitrosamines. These substances can promote the development of cancer, and above all they increase the risk of colon cancer. Methods such as curing and intense heating are particularly used for industrially processed meat, such as sausage and ham. Accordingly, processed meat products are particularly unhealthy.

8. Avoiding meat makes you slim

Researchers at the Max Planck Institute for Cognitive and Neurosciences (MPI CBS) and the Leipzig University Hospital examined almost 9,000 people, what connections there are between body and mind on the one hand and not consuming animal products on the other. regardless of age, gender and level of education. The study was published in June 2020 in the specialist magazine “Nutrients”.

The result of the physical impact: the less food of animal origin was on the menu, the lower the average body mass index (BMI) and thus the body weight. “Products that are excessively high in fat and sugar make you fat. They stimulate the appetite and delay the feeling of satiety. If you do without animal foods, you eat fewer such products on average, ”explains Evelyn Medawar, first author of the work.

9. Avoiding meat and the psyche

With regard to the psychological effects of the meatless diet, the Leipzig study found no particular susceptibility to neuroses in vegetarians. The study director Veronica Witte says: “Previous analyzes had found that more neurotic people generally leave out certain food groups more often. We focused solely on avoiding animal products and could not observe any correlation. ”No connection was found between a predominantly plant-based diet and depressive moods. There was evidence of this in previous studies.

However, the researchers found a difference in one of the determining factors of personality: the extroversion or introversion. People with predominantly plant-based foods on the menu are more introverted than those who eat primarily animal products. The study authors have not yet found an explanation for this.