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.

Small bowel cancer accounts for up to five percent of all bowel cancers; around 2,600 men and women were diagnosed with small bowel cancer in 2016, compared with around 60,000 colon cancer. “It is important to classify a carcinoma on the one hand by localization, i.e. in the case of bowel cancer, small or colon cancer, but also differentiate it on the basis of its biological characteristics,” reports Ulrich Graeven, chief physician at the Clinic for Hematology, Oncology and Gastroenterology at Maria Hilf Mönchengladbach Hospital.

Cancer of the small intestine is usually biologically very different from cancer of the colon

While colon cancer is usually adeno tumors, i.e. growths of the mucous membrane, this affects only a small fraction of small bowel cancer. The most common forms of small bowel cancer, depending on the cells that cause the disease, are:

• Neuroendocrine tumors (NET) with around 50 percent, they arise from hormone-producing cells
• Gastrointestinal stromal tumors (GIST) make up about ten percent, these tumors originate from the connective tissue in the gastrointestinal tract.

The differing biological characteristics of the two types of colon cancer, colon and small bowel cancer, “make these two diseases so fundamentally different, even though both affect the bowel,” explains the oncologist.

Causes of small bowel cancer and why it is less common than colon cancer

What triggers the fact that the cells in the small intestine no longer act normally, but degenerate and multiply in an uncontrolled manner, is still largely unknown. It is assumed that there is a connection with pollutants in food that come into contact with the small intestine during passage and can thus influence its cells.

It is well known that the small intestine connects directly to the stomach. This first section of the three-part small intestine is called the duodenum, followed by the jejunum and ileum. In addition to transporting the chyme to the large intestine, the task of the five-meter-long small intestine is to break down certain food components and release them into the blood. The most important ones are carbohydrates, which are processed into various sugars, fat, but also vitamins and trace elements.

The chyme is still thin in this section of the intestine and is therefore transported on quickly. The contact time with the intestinal wall is much shorter than later in the large intestine, “which could explain why colon cancer is much more common than small intestine cancer,” the gastroenterologist explains the possible background. In addition, the mucous membrane in the small intestine is less susceptible to certain factors such as pollutants than that in the large intestine.

Risk factor hereditary diseases

However, there is also a familial willingness to develop small bowel cancer: Hereditary polyposis syndromes such as familial adenomatous polyposis (FAP) and Lynch syndrome. Genetically, a large number of polyps develop in the large intestine, sometimes also in the small intestine. These are adenocarcinomas, but are very rare in the small intestine compared to NET and GIST.

Small intestinal tumors associated with FAP are usually only discovered when polyps have been detected in the large intestine. In the course of further diagnosis of the familial predisposition, these rare small bowel carcinomas are also identified.

Small bowel cancer symptoms

Small bowel cancer usually grows slowly. Frequently, signs only appear when the disease has progressed and the tumor is taking up space. Depending on you can

• Bleeding,
• Stomach pain,
• nausea
• Constipation or diarrhea

occur. If the tumor is large, it can even block the intestines (ileus). The intestinal obstruction manifests itself through massive pain, it is always a medical emergency that is life-threatening and must be treated immediately.

Small bowel cancer prognosis varies

Small bowel cancer is usually only discovered at an advanced stage. In more than 70 percent, the carcinoma is only diagnosed in stage three or four, i.e. later than this applies to this common colon cancer – again the comparison with colon cancer.

The survival rates for small bowel cancer are therefore somewhat lower. “The decisive factor, however, is always the type of cancer of the small intestine,” explains the expert. If a GIST or NET is detected early, the chances of survival are very good. If, on the other hand, it is adenocarcinoma, which is also usually discovered later, the prognosis is not quite as favorable.

Diagnosis of small bowel cancer

The classic examination methods of gastroscopy and colonoscopy only cover the upper or lower part of the small intestine, “the almost five meters in between are not reached with these examination techniques,” explains the expert.

Imaging methods such as magnetic resonance tomography (MRT) or computed tomography (CT) are only used if there are symptoms and suspicion of this intestinal tumor. Capsule endoscopy, which shows images from the small intestine, also provides information.

Only when these examinations reveal an abnormality is it possible to specifically mirror the small intestine. “However, this is very time-consuming and cannot be used as a preventive examination – also because these intestinal tumors are very rare,” emphasizes Ulrich Graeven.

Small intestinal cancer therapies – surgery and its consequences

Overall, the following applies to the various small intestinal tumors: If possible, an operation should be performed. “If the tumor is limited, parts of the small intestine can usually be removed without any problems,” explains the oncologist in more detail.

A stoma, i.e. an artificial anus, is therefore usually not necessary. However, it is crucial which part of the small intestine is missing and which functions it had, which trace elements and vitamins it passed on to the body. This deficiency must then be compensated for through appropriate nutrition or medication.

Treatment for small bowel cancer varies depending on the type of tumor

Parts of the removed tumor are examined histologically. For the therapy plan, it is crucial whether it is NET, GIST or the rare familial adenocarcinoma in the small intestine. “A generally applicable therapy scheme for small bowel cancer is not possible because there is not just one small bowel cancer, but different ones, it always depends on its type,” emphasizes the oncologist.

Accordingly, there are many different therapy options. If a gastrointestinal stromal tumor (GIST) has metastasized, for example, there are very good drugs for further treatment. “This is not the classic chemotherapy, but we use so-called tyrosine kinase inhibitors, with very good results,” reports the expert. These are inhibitors, such as imitanib, that can block certain signaling pathways within the cells. They are sometimes also used before an operation to reduce the size of a tumor that is too large and therefore inoperable, or after an operation to avoid a relapse.

If the cancer of the small intestine is a neuroendocrine tumor (NET), on the other hand, surgery is often the only treatment required. The NET is further subdivided with regard to the need for drug therapy, taking into account its growth rate. This subdivision of the NET is also of crucial importance for planning therapy for metastatic NET.

Ademocarcinoma of the small intestine is treated on the basis of the results from the treatment of colon tumors.

Small bowel cancer prevention

Targeted prevention against these rare tumors is hardly possible – apart from the well-known rules for a healthy life, i.e. without smoking, with a sensible diet, extensive alcohol restriction and sufficient exercise. Because little is known about the possible causes of small bowel cancer, they cannot be influenced.

However, there is an important tip from the expert for everyone in whose families there are genetically determined polyps in the large intestine: Remember to not only limit the preventive measures to the large intestine, but also to extend it to the small intestine. Although this is provided for in the relevant colorectal cancer screening and follow-up programs, it must not be overlooked.