tumors

cholangiocarcinoma

Generality

Cholangiocarcinoma is the serious malignant tumor that originates from the rapid and uncontrolled replication of an epithelial cell of the bile ducts, ie the channels that carry bile from the liver to the duodenum.

Although the precise causes of cholangiocarcinoma are unknown, doctors believe that factors such as: primary sclerosing cholangitis, congenital anomalies of the bile ducts, some parasitic infections affecting the liver, exposure to certain chemicals, smoking, liver cirrhosis, etc.

Almost never symptomatic in the beginning, cholangiocarcinoma causes in its most advanced phases some characteristic symptoms, including: jaundice, abdominal pain, itchy skin, light stools, loss of appetite, loss of body weight, fatigue and fever; always in its most advanced stages, then, it can disseminate its cancer cells elsewhere and cause secondary malignant tumors.

Possible treatments that can be used in the case of cholangiocarcinoma include surgical removal of the tumor, radiotherapy and chemotherapy.

Brief review of what the bile ducts and bile are

The bile ducts (or bile ducts ) are the channels responsible for transporting bile from the liver to the gall bladder and from the gall bladder to the duodenum (intestine tract).

Secreted by the liver, bile is the liquid substance that, during the digestive process, has the important task of facilitating the digestion of fats.

What is cholangiocarcinoma?

Cholangiocarcinoma is a malignant tumor (or malign neoplasm) originating from the rapid and uncontrolled proliferation of one of the epithelial cells that make up the bile ducts.

Cholangiocarcinoma is an example of adenocarcinoma ; adenocarcinomas are particular malignant tumors of the genus carcinoma, which originate from the uncontrolled multiplication of an epithelial cell of a secretory glandular organ (eg, pancreas) or tissue with secretory properties.

Epidemiology

Cholangiocarcinoma is a fairly rare tumor; according to statistics, in fact, in the so-called Western World it would have an annual incidence of 1-2 cases per 100, 000 people. However, it is important to point out that in the last few decades, in North America, Europe and Australia, there has been a not inconsiderable increase in the annual number of cholangiocarcinoma cases.

Cholangiocarcinoma is a malignant tumor that affects older people more frequently: in this respect, the numbers say that 2 out of 3 patients (so about 67% of patients) are over 65 years old.

Causes

Like many other malignant tumors, cholangiocarcinoma is also the result of a slow accumulation by the cell from which it originates of genetic mutations, which alter the normal processes of reproduction and cell growth.

Currently, doctors ignore the precise causes of the aforementioned mutations; however, through numerous studies, they believe with a certain degree of certainty that they have identified several risk factors (ie factors that favor the onset of cholangiocarcinoma).

Main risk factors of cholangiocarcinoma: what are they?

According to the doctors, cholangiocarcinoma risk factors are important:

  • The presence of the so-called primary sclerosing cholangitis . Primary sclerosing cholangitis is a serious chronic inflammatory disease, which first causes a stenosis of the intrahepatic bile ducts (ie the bile ducts that pass through the liver) and subsequently liver cirrhosis and liver failure .

    According to experts, primary sclerosing cholangitis is the most important risk factor for cholangiocarcinoma in Western world countries.

  • Congenital anomalies in the bile ducts . Among the possible congenital anomalies affecting the bile ducts, the one most commonly associated with the development of cholangiocarcinoma is the so-called Caroli syndrome .

    Caroli syndrome is a hereditary disease, characterized by cystic dilatation of the intrahepatic bile ducts, which over time produces phenomena such as portal hypertension and liver fibrosis.

  • The presence of intrahepatic gallstones ( intrahepatic biliary lithiasis ). Gallstones are small solid aggregates, similar to pebbles, which are formed as a result of the abnormal precipitation of some substances typically contained in bile.

    Gallstones are called intrahepatic, when their location is at the level of the intrahepatic bile ducts.

  • Exposure to certain chemicals and toxins . Among the chemical substances imputed to favor the appearance of cholangiocarcinoma, there is also the torotrasto, a particular suspension based on thorium dioxide, which before the discovery of its carcinogenic power (1930s-1940s), was used as a means of contrast in different X-ray diagnostic procedures.
  • Parasitic (parasitic) infections of the liver supported by Opistorchis viverrini or Clonorchis sinensis . Examples, respectively, of opisthorchiasis and clonorchiasis, the aforementioned parasitoses are quite rare in the world, except in Asia, to be precise in countries such as Thailand, Taiwan, China, Eastern Russia, Korea, Vietnam and Laos).

Other risk factors of cholangiocarcinoma

The list of cholangiocarcinoma risk factors also includes conditions and behaviors, such as:

  • Hepatitis B and hepatitis C. Both are infectious diseases of the liver of viral origin;
  • Liver cirrhosis;
  • Lynch II syndrome;
  • Diabetes mellitus;
  • Obesity;
  • Excessive alcohol consumption;
  • Cigarette smoke.

Symptoms and Complications

To learn more: Symptoms Cholangiocarcinoma

When it reaches certain dimensions, cholangiocarcinoma blocks the flow of bile along the biliary tract; this causes the bile to rise in the direction of the liver (which is the organ from which it comes) and that the substances contained in it pass into the blood (thus making them the protagonists of a completely anomalous and non-physiological phenomenon).

The symptoms of cholangiocarcinoma depend on the rise of bile to the liver and the passage of substances contained in bile into the blood, which are:

  • Jaundice. It is the most characteristic symptom;
  • Skin itching. It affects 66% of patients;
  • Light feces and dark urine;
  • Loss of appetite and weight loss. Between 30 and 50 patients lose weight every 100 (30-50%);
  • Persistent fatigue and malaise;
  • Abdominal pain and swelling (usually on the upper right side of the abdomen).

    Abdominal pain characterizes 30-50% of clinical cases;

  • Fever at 38 ° or higher. Fever is a symptom that affects 20% of cholangiocarcinoma patients;
  • Chills.

Cholangiocarcinoma is a subtle disease

Cholangiocarcinoma is a subtle disease, because it shows signs and symptoms only at a certain stage of progress and when it has reached such dimensions as to considerably reduce the success of a possible therapy.

When should I go to the doctor?

The presence of jaundice is always a more than valid reason to contact your treating physician with some care or to go to the nearest hospital center for investigations.

The causes of jaundice are numerous and, since some of these are very dangerous conditions (the cholangiocarcinoma is an example), their precise identification has a decidedly important importance.

Complications

In more advanced stages, a malignant tumor such as cholangiocarcinoma has the ability to spread its cancer cells - through blood, lymph or contiguity - to other organs and tissues of the human body (liver, lungs, brain, bones, etc.), causing the formation of secondary malignancies in these "new" anatomical sites.

The spread of their cells elsewhere by a malignant tumor is a phenomenon with often unfortunate consequences.

Readers are reminded that the cells scattered by a malignant tumor in other sites are the sadly known metastases .

Diagnosis

In general, diagnostic investigations for the detection of a cholangiocarcinoma begin with a careful medical history and an accurate physical examination ; therefore, they continue with a blood test and a series of diagnostic imaging tests ; finally, they end with a tumor biopsy .

Unfortunately, due to the lack of early symptoms, early diagnosis of cholangiocarcinoma is quite complex; in fact, diagnoses often occur when the cancer is already at an advanced stage and there is little hope of successfully treating the disease.

Physical examination and medical history

Physical examination and anamnesis consist essentially in the observation and critical study of the symptoms manifested by the patient; as a rule, they constitute the first step of the examination and test procedure which will then lead to the definitive diagnosis of cholangiocarcinoma.

Blood analysis

For a patient with all the typical symptoms of a cholangiocarcinoma, blood tests are used to evaluate:

  • Liver function;
  • The presence of a tumor marker, called CA19-9, typical of malignant tumors of the bile ducts and malignant tumors of the pancreas (NB: in patients with these tumors, CA 19-9 is present in quantities higher than normal in 9 cases every 10).

Diagnostic imaging

The diagnostic imaging tests allow to establish with precision the site and the dimensions of the cholangiocarcinoma (see table on the types of cholangiocarcinoma).

The list of diagnostic imaging exams useful for the study of a cholangiocarcinoma include:

  • Abdominal ultrasound;
  • The magnetic resonance of the abdomen;
  • Abdominal CT;
  • Endoscopic retrograde cholangiopancreatography, better known as cholangiopancreatography or ERCP;
  • Percutaneous transhepatic cholangiography;
  • Endoscopic ultrasound. .
Table. Types of cholangiocarcinoma
GuyFeatures
Intrahepatic cholangiocarcinomaThe tumor is located in the bile ducts passing through the liver (intrahepatic bile ducts).

For some experts, it is a liver tumor.

Hilar cholangiocarcinoma (or Klatskin's tumor)The tumor is located in the bile ducts just outside the liver.
Distal cholangiocarcinomaThe tumor is located in the bile ducts near the duodenum

Tumor biopsy

The tumor biopsy consists in the collection and in the histological analysis, performed in the laboratory, of a sample of cells from the tumor mass.

Tumor biopsy is important, because - in addition to representing a diagnostic test confirming all previous observations - it also allows to establish the degree of malignancy and staging of a cholangiocarcinoma, ie the two parameters through which doctors judge the severity of the neoplasia present.

What are staging and the degree of a malignant tumor?

The staging of a malignant tumor includes all that information, collected during biopsy, which concerns the size of the tumor mass, its infiltrating power and its metastasizing capacities.

The degree of a malignant tumor, on the other hand, includes all those data that emerged during the biopsy, which concern the extent of transformation of malignant tumor cells, compared to their healthy counterparts.

HOW THE SAMPLING OF THE CELL SAMPLE IS

As a rule, doctors take the cell sample from a cholangiocarcinoma, using the canonically used instruments during a cholangiopancreatography or a percutaneous transhepatic cholangiography. In other words, to obtain the sample of tumor cells to be analyzed in the laboratory, doctors use cholangiopancreatography or percutaneous transhepatic cholangiography.

Therapy

The therapy of cholangiocarcinoma depends on at least 4 factors, which are: the staging and the degree of malignancy of the tumor (therefore size of the tumor mass, presence of metastases, progression of the disease etc.), the position of the tumor and the general state of health of the patient .

Currently, the therapeutic options available to a cholangiocarcinoma sufferer are:

  • The tumor removal surgery;
  • Radiotherapy;
  • Chemotherapy;
  • Biliary stenting and biliary drainage via bypass

The when and the why the doctors resort to one or more of the aforementioned treatments will be discussed in the next chapters.

Surgical removal of the tumor

Surgical removal of cholangiocarcinoma is the most effective treatment for healing; unfortunately, however, it is applicable and can be effective only when the tumor is small or, in any case, has only slightly affected the neighboring organs and lymph nodes.

Surgery to remove a cholangiocarcinoma may include:

  • The removal of the bile duct from the neoplasm site, followed by the reconnection of the resulting stumps, so as to reconstitute the continuity of the biliary tract.

    Exploitable only when the tumor is small, this type of intervention is minimally invasive;

  • Removal of the bile duct that houses the tumor and the portion of the liver in which the tumor has spread. Also in this case, the operating surgeon must provide to restore the continuity of the remaining bile ducts;
  • The removal of the bile ducts, the duodenum tract connected to the stomach and bile ducts (C duodenal), the portion of the stomach joined to the duodenal C, the pancreas, the gall bladder and the regional lymph nodes (ie the lymph nodes located near these organs ).

    Known as a Whipple procedure, this so invasive operation is reserved for cases of severe cholangiocarcinoma which, however, can still benefit from the benefits of surgery.

Radiotherapy

Radiation therapy involves exposing the tumor mass to a certain dose of high-energy ionizing radiation (X-rays), which are intended to destroy neoplastic cells.

In the case of cholangiocarcinoma, radiotherapy may represent:

  • A form of post-surgical treatment ( adjuvant radiotherapy ). The purpose of adjuvant radiotherapy is to destroy tumor cells with X-rays, which the surgery has not removed.
  • A form of alternative treatment to surgery, when the latter is impractical due to an advanced tumor. Normally, in these situations, radiotherapy plays the role of symptomatic therapy, aimed at lightening the patient's suffering.

Curiosity

Cholangiocarcinoma is a malignant tumor that can be treated with a particular form of radiotherapy, known as brachytherapy or internal radiotherapy .

Chemotherapy

Chemotherapy consists of the administration of drugs capable of killing rapidly growing cells, including cancer ones.

In the presence of cholangiocarcinoma, chemotherapy may constitute:

  • A form of post-surgical treatment ( adjuvant chemotherapy ). The aim is the same as for adjuvant radiotherapy: to destroy cancer cells not eliminated by surgery;
  • A form of alternative treatment to surgery, when the latter is not applicable due to an advanced stage tumor. In general, in these circumstances, chemotherapy is used to alleviate the symptoms of an incurable pathological condition.

Biliary stenting

Biliary stenting is the surgical operation that allows the elimination of a narrowing or a "block" in a bile duct, through the insertion in the latter of a plastic tube, metal or other special material. The purpose of this operation is to re-establish, at least in part, the flow of bile within the bile ducts.

In the case of cholangiocarcinoma, biliary stenting is used as a symptomatic treatment, when the tumor is in an advanced stage and cannot be surgically removed.

Biliary drainage through bypass

Biliary drainage through bypass is the surgical procedure that allows you to bypass an obstacle or blockage within the bile ducts by creating an alternative route.

The purpose of biliary drainage through bypass is, clearly, to restore the discharge of bile into the duodenum.

In the case of cholangiocarcinoma, biliary drainage through bypass has the same indications as biliary stenting : it is a symptomatic treatment, used when the tumor is in an advanced stage and cannot be removed by surgery.

Curiosity

In the case of cholangiocarcinoma, biliary stenting, biliary drainage through bypass, symptomatic radiotherapy and symptomatic chemotherapy are the so-called palliative care of the disease in question.

Prognosis

The prognosis in the case of cholangiocarcinoma depends on how timely the diagnosis is (an early diagnosis is associated with a greater probability of recovery) and the site of the tumor (some bile ducts lend themselves better to therapies than others).

According to the most recent statistical studies:

  • For people with a cholangiocarcinoma at a fairly early stage, the 5-year survival rate from the diagnosis is between 20 and 50%;
  • For individuals with a cholangiocarcinoma at an operable stage only by the Whipple procedure, the 5-year survival rate from the diagnosis is 15%;
  • For people with advanced non-surgically removable cholangiocarcinoma, the 5-year survival rate is 2%.