Chief of Surgery Prof. Dr. med. Thomas Gruenberger is a renowned specialist in liver, pancreas, and biliary tract surgery and is considered one of the leading specialists in the field of oncological surgery in Vienna. As head of the Department of Surgery at Favoriten Hospital—one of Austria’s leading centers for the treatment of liver, pancreas, and biliary tract tumors—Prof. Dr. Gruenberger is deeply committed to treating complex tumor diseases. In addition to his clinical work, he also serves as chair of HPB surgery (hepato-pancreato-biliary surgery) at Sigmund Freud Private University in Vienna, where he makes a significant contribution to the advancement of teaching and research in visceral surgery through his collaboration with Vienna’s hospitals.
Prof. Dr. Gruenberger’s expertise encompasses, in particular, the surgical treatment of liver tumors, liver metastases, pancreatic cancer, gallbladder carcinomas, and bile duct carcinomas. Since 1998, Prof. Dr. Gruenberger has focused on liver and pancreatic surgery and has successfully performed over 3,000 liver surgeries and more than 700 pancreatic procedures during his career. This extensive experience, which he has gained at renowned hospitals, including some in Australia, makes him a highly sought-after expert in tumor surgery. One of his core areas of expertise is liver resection, a surgical procedure that may be necessary for both benign and malignant liver diseases. Even in cases of liver metastases—which develop as secondary tumors from primary tumors—Prof. Dr. Gruenberger evaluates the possibility of surgical removal, provided it is beneficial for the patient.
In addition to traditional surgical techniques, Prof. Dr. Gruenberger also offers minimally invasive, robot-assisted procedures at Klinikum Favoriten. Another focus of his work is the surgical treatment of pancreatic tumors, particularly partial or total pancreatectomy. In these procedures, Prof. Dr. Gruenberger selectively removes the tumor-bearing portion of the pancreas and restores the function of the adjacent organs through careful surgical anastomoses to ensure normal digestion.
In addition to his clinical work, Prof. Dr. Gruenberger is also active in research and has authored numerous scientific publications that have contributed to his international reputation. He is also a member of the Austrian Society for Surgical Oncology (ASSO) and the European Society of Surgical Oncology (ESSO), and is actively involved in several other surgical and medical oncology professional societies. He regularly shares his expertise as a sought-after speaker at national and international conferences and through the training of future physicians and nurses. Prof. Dr. Gruenberger always develops treatment plans in close collaboration with an interdisciplinary team of specialists from other fields in order to offer each patient a tailored and promising therapy.
The editorial team of the Leading Medicine Guide had the opportunity to speak with Prof. Dr. Gruenberger, focusing on cholangiocellular carcinoma (CCA), a malignant tumor that originates in the bile ducts, also known as bile duct carcinoma.
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Bile duct carcinoma is a rare form of cancer that originates in the bile ducts. The bile ducts are thin tubes that carry bile from the liver to the intestines, where it aids in the digestion of fats. This tumor can develop either within the liver (intrahepatic) or outside the liver (extrahepatic). Although the disease is rare, it is particularly dangerous because it is often not detected until advanced stages, when it has already spread to other organs. The exact causes are not yet fully understood, but certain risk factors, such as chronic inflammation of the bile ducts and certain liver diseases, increase the likelihood of developing cholangiocellular carcinoma. Treatment options depend on the stage of the disease and include surgery, chemotherapy, and, in some cases, radiation therapy.
Prof. Dr. Gruenberger explains at the beginning of our conversation: “In recent years, we have observed an increase in cholangiocellular carcinoma. Compared to hepatocellular carcinoma (HCC), I note that in 2024 we performed surgery on about three times as many patients with cholangiocellular carcinoma. This is certainly also due to improved diagnostics and not solely to a higher prevalence of this type of cancer. However, it is extremely important to raise awareness about bile duct carcinoma, which can occur in four different types:
- Intrahepatic carcinoma, which originates within the liver.
- Klatskin tumor, which is located in the area of the hepatic portal (hilar cholangiocarcinoma). These tumors pose a particular challenge for surgeons because they are situated at the confluence of the bile ducts and require major surgery.
- Distal bile duct carcinoma, which is located near the opening of the bile duct (ductus choledochus) into the duodenum.
- Gallbladder carcinoma.
These four types are significantly more common in our practice than hepatocellular carcinoma. In the case of HCC, the situation has improved due to advances in hepatitis C therapy, as the infection is now curable or, at the very least, manageable in its chronic form. This represents a significant change compared to earlier textbook opinions.”
Regarding the risk factors for bile duct carcinoma, Prof. Dr. Gruenberger adds: “Risk factors for bile duct carcinoma are more difficult to identify than for hepatocellular carcinoma, where alcohol, fatty liver, and cirrhosis are clearly the primary factors. These factors play a minor role in bile duct carcinoma. Patients with primary sclerosing cholangitis or inflammatory bowel diseases such as ulcerative colitis are at increased risk. It is well known that gallbladder cancer is almost always associated with gallstones, although the incidence of gallbladder tumors is extremely low compared to that of gallstones.”
The symptoms of cholangiocarcinoma often develop gradually and frequently go unnoticed in the early stages, which makes timely diagnosis difficult.
Prof. Dr. Gruenberger explains: “Symptoms vary depending on the tumor’s location. Jaundice (icterus) often occurs—recognizable by the yellowing of the skin and eyes—when the tumor blocks the flow of bile. This is typical of a Klatskin tumor or distal CCA. Intrahepatic tumors, on the other hand, are often discovered incidentally, for example during a CT scan performed for another reason. In the case of gallbladder cancer, it is not uncommon for the diagnosis to be made only after a cholecystectomy performed due to gallstones, through pathological examination of the tissue. Larger tumors become symptomatic due to their expansion.”
In addition to these specific symptoms, patients may experience fatigue, unintentional weight loss, and pain in the upper abdomen. This pain, which often radiates to the back, usually occurs when the tumor is larger or is affecting neighboring organs. Impaired bile flow can also lead to digestive problems and loss of appetite. Since these symptoms can also occur with other conditions, a comprehensive medical evaluation is crucial for establishing a clear diagnosis.
Bile duct cancer is diagnosed through a series of tests designed to identify the tumor, determine its exact location, and assess the stage of the disease.
The first steps often include a thorough physical examination and a review of the patient’s medical history, especially if symptoms such as jaundice, upper abdominal pain, or weight loss are present. Blood tests are also common to check liver function and specific tumor markers. Tumor markers such as CA 19-9 or CEA may be elevated, but they are not specific to bile duct cancer and serve more as an indicator. Imaging tests are crucial for the accurate diagnosis and staging of bile duct cancer. An ultrasound examination can reveal early signs of bile duct narrowing or bile stasis. Computed tomography (CT) and magnetic resonance imaging (MRI) provide detailed insights into the size and location of the tumor, as well as any possible spread to neighboring organs or lymph nodes. A specialized MRI technique called MRCP (magnetic resonance cholangiopancreatography) provides detailed images of the bile ducts and the pancreas and helps locate the tumor. In some cases, endoscopic retrograde cholangiopancreatography (ERCP) is also performed, in which a contrast agent is injected into the bile ducts using an endoscope to visualize their structure under X-ray guidance. During ERCP, tissue samples can also be taken for histological examination to confirm the cancer diagnosis. Bile duct tumors can be visualized in even greater detail using a procedure known as a “spyglass” examination, in which a small camera is inserted directly into the bile duct.
“The difficulty of diagnosis depends heavily on the type of tumor. In the case of distal bile duct carcinoma, due to its location near the papilla—where the bile duct and pancreatic duct converge—diagnosis is ideally performed via endosonography, in which a biopsy is obtained from the tumor under ultrasound guidance. The easiest to diagnose is the intrahepatic tumor, which originates directly in the liver. This type of tumor often shows a characteristic pattern on imaging and makes a biopsy unnecessary if it is deemed operable by the tumor board in the presence of a liver surgeon. It is also characterized by a variety of molecular biological markers that can be used to guide specific therapies. Each tumor cell possesses different receptors or “sensors,” which are analyzed to determine whether targeted therapy is possible. The standardized first-line therapy consists of a combination of chemotherapy and immunotherapy. For about half of the patients, this therapy is insufficient because the tumor exhibits molecular pathological alterations that require individualized drug treatment. IDH1 therapy and FGFR2 therapy have been particularly successful over the past two years. However, since up to 17 different molecular alterations can occur in liver tumors, standardized treatment is not possible. For this reason, a specific molecular pathological examination is necessary, which should ideally be performed at the time of diagnosis. In most cases, these therapies cannot replace surgery. If the patient is a candidate for surgery, the procedure is performed, followed by six months of adjuvant therapy administered orally. “Unfortunately, about half of the patients must still expect a recurrence,” said Prof. Dr. Gruenberger.
IDH1 (isocitrate dehydrogenase 1) therapy is a targeted treatment for liver tumors, particularly bile duct carcinomas, that harbor an IDH1 mutation. This mutation leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG), which promotes tumor growth. IDH1 inhibitors such as ivosidenib block the mutated enzyme and reduce 2-HG, thereby slowing tumor progression. The therapy is primarily used for advanced or inoperable tumors and generally has fewer side effects than chemotherapy. However, it is effective only in tumors with a confirmed IDH1 mutation.
FGFR2 therapy (Fibroblast Growth Factor Receptor 2) is a targeted treatment for certain bile duct carcinomas that exhibit alterations in the FGFR2 gene (Fibroblast Growth Factor Receptor 2), such as fusions or mutations. These genetic alterations lead to overactivation of the FGFR2 signaling pathway, which promotes tumor growth. FGFR inhibitors, such as pemigatinib or futibatinib, block this signaling pathway to slow or stop the growth of tumor cells. This therapy is primarily used in patients with advanced or metastatic tumors when surgery is not an option and genetic testing confirms the FGFR2 alteration. Side effects may occur but are often manageable.
To ensure complete tumor removal, the surgeon often must remove parts of the liver while preserving the integrity of the blood vessels. Such procedures require a high degree of precision and can only be performed at specialized centers.
“The greatest challenge is to preserve sufficient functional liver tissue for the patient following liver surgery. Intrahepatic carcinoma, Klatskin tumor, and gallbladder carcinoma are typically treated with a liver resection combined with a bile duct resection. Distal bile duct carcinoma, on the other hand, requires a pancreatic head resection (Whipple procedure). All of these procedures are major and complex surgeries associated with a high risk of complications. Therefore, they should be performed exclusively in specialized centers with extensive experience and routine in such procedures. Intrahepatic carcinoma often grows near major vessels such as the portal vein or the hepatic veins, which frequently necessitates a major resection. The so-called Future Liver Remnant (FLR) describes the functional and anatomical portion of the liver that remains after a planned resection. This portion must be large enough to continue performing vital functions such as detoxification, metabolic regulation, and protein synthesis. “In healthy patients, the FLR should account for at least 30% of the original liver volume, while in patients with liver damage—such as those with fatty liver or fibrosis—it must be at least 40%,” explains Prof. Dr. Gruenberger, adding important information about liver volume:
“In a healthy liver, the Future Liver Remnant (FLR) should account for at least 30% of the original liver volume. In very young patients, whose livers have a high capacity for regeneration, a proportion of 25% may be sufficient. However, a damaged liver, such as one affected by fatty liver disease or fibrosis, has limited functional capacity. In such cases, the FLR must be significantly larger—at least 40%—to prevent liver failure after surgery. Before surgery, the FLR is precisely calculated using CT volumetry. This involves measuring the total volume of the liver, which averages about 1,500 ml in an adult. Based on this, it is determined which portions can be resected without the remaining volume becoming too small. If it becomes apparent that the planned residual portion of the liver is insufficient for the patient, the liver is specifically enlarged prior to surgery. This is achieved, for example, through portal vein embolization or sequential double embolization, in which the blood flow (portal vein) and outflow (hepatic veins) to the section of the liver to be removed are occluded by interventional radiologists, causing more blood to flow into the portion of the liver to be preserved. This stimulates the growth of the remaining portion of the liver. Within a few days to about a week, the FLR may increase significantly, allowing the surgery to proceed. A liver resection is always a challenging surgery and typically lasts several hours. If a bile duct resection is also required, which involves reconstruction of the bile ducts, the duration of the surgery is extended. In particularly complex cases or if unexpected difficulties arise, the surgery can take the entire day.”
Robotic Surgery
“It is important to note that the difference between open and minimally invasive surgery is significant. Although minimally invasive procedures—especially those performed with robotic assistance—typically take longer than open procedures, they offer patients significant advantages. Patients generally recover faster, experience less pain, have smaller scars, and there is less blood loss during the operation. Many patients report as early as the day after the procedure that they don’t actually feel as though they’ve undergone major surgery. From a surgical perspective, robotic surgery offers significant advantages. It enables more precise tumor removal, improved visibility through high-resolution 3D imaging, and greater freedom of movement for the instruments. However, the key factor is the benefit to the patient, particularly in the form of a faster recovery and improved postoperative well-being. The oncological prognosis depends largely on the quality of the surgery and the complete removal of the tumor. Minimally invasive techniques, including robotic surgery, have shown comparable or slightly improved outcomes in some studies. However, they are particularly beneficial when performed by experienced surgeons,” comments Prof. Dr. Gruenberger on the topic of robot-assisted surgery.
Under certain conditions, a liver transplant may be a treatment option for patients with bile duct carcinoma, particularly in cases of perihilar cholangiocarcinoma (Klatskin tumor), which is located in the area of the bile duct bifurcation at the hepatic hilum, where the bile ducts from the right and left lobes of the liver converge.
While these tumors are often considered locally inoperable, studies show that selected patients may have an improved prognosis with a liver transplant combined with preoperative radio- and chemotherapy. However, this treatment option is only suitable for a very small, carefully selected group of patients, as specific criteria must be met to maximize the chances of success and minimize the risk of recurrence.
“There is a comprehensive protocol for Klatskin tumors from the U.S.—specifically the Mayo Clinic—that is used at only a few centers worldwide. However, it is not the case that a patient is simply diagnosed and then placed on a waiting list. Before a potential liver transplant, the patient must undergo chemotherapy; the tumor is irradiated both internally and externally; and the patient must also undergo surgical exploration to confirm that the tumor has metastasized only locally to the bile duct and not to the lymph nodes. Patients who do not qualify for a transplant but have undergone all the preceding treatments have a poor prognosis due to the extent of their prior treatment. “Those who qualify for a transplant have an exceptionally good outcome, with a 5-year survival rate of approximately 75%. For other bile duct tumors, there are currently no established transplant protocols,” states Prof. Dr. Gruenberger.
The well-established HPB Center in Vienna, led by Prof. Dr. Gruenberger, performs the most liver resections in Austria (approximately 130 liver resections per year); in addition, around 50 pancreatic resections are performed annually.
For people at increased risk of bile duct carcinoma—such as those with chronic liver disease, primary sclerosing cholangitis (PSC), chronic inflammation of the bile ducts, or a genetic predisposition, preventive measures and regular screenings are crucial for detecting the disease early or potentially preventing it.
A healthy lifestyle—including a balanced diet, avoiding tobacco use, and limiting alcohol consumption—can reduce the risk of liver disease and inflammation of the bile ducts. Vaccination against hepatitis B and, if necessary, treatment for chronic hepatitis C are important preventive measures, as chronic liver inflammation increases the risk of bile duct cancer. For individuals with gallbladder polyps, who are at increased risk for gallbladder cancer, gallbladder removal should be considered to prevent potential tumor formation.
“Only high-risk patient groups known to have liver disease or inflammatory bowel disease can take preventive action—they should undergo imaging every six months. For example, a patient with chronic cholangitis (inflammation of the bile ducts) should undergo regular CT scans. For the general population, there are no preventive measures. Here, each person must decide for themselves how to shape their ‘lifestyle’—those who drink alcohol very frequently, are physically inactive, and eat an unhealthy diet naturally have an increased risk of developing liver cancer,” warns Prof. Dr. Gruenberger, and with that, we conclude our interesting conversation.
Thank you very much, Professor Dr. Gruenberger, for this insightful look into liver surgery!
