Gallbladder cancer

Among all malignant neoplasms of internal organs, cancer of the gallbladder, extrahepatic ducts and pancreas constitute a special group. Their unification is due to localization in one anatomical zone, the uniformity of the functional and structural changes they cause, as well as the similarity of pathogenetic mechanisms, clinical manifestations, complications and treatment methods.

In the general structure of oncological pathology, gallbladder cancer is not common and accounts for no more than 4-6%. In this regard, many doctors, and especially students, do not know the specifics of its detection and treatment.

Gallbladder cancer ranks 5th-6th in the structure of malignant neoplasms of the gastrointestinal tract; its share in the structure of all malignant tumors does not exceed 0.6%.

Gallbladder cancer most often occurs in women over 40 years of age against the background of gallstone disease.

Malignant neoplasms of the extrahepatic ducts and the large duodenal papilla are rare, but more common than gallbladder cancer. They account for 7-8% of all malignant tumors of the periampullary zone and 1% of all neoplasms. Gallbladder cancer can be localized in any part of the ducts: from the porta hepatis - Klatskin tumor (56.3% of cases) to the terminal part of the common duct (43.7% of cases).

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What causes gallbladder cancer?

The progressive deterioration of the environmental situation, the lack of a rational nutrition system, the increase in household hazards, including smoking and alcohol consumption, contribute to the steady increase in the number of patients in this group.

What causes gallbladder cancer is still unknown. At present, it is difficult to identify the etiological factor in each patient, so when searching for people with an increased risk of developing a neoplastic process, those conditions that most often contribute to the implementation of the oncogene are taken into account. These include the following risk parameters:

• there are unambiguous opinions about the role of food products in the development of neoplasms, in particular the consumption of animal proteins and meat, as well as the content of saturated and unsaturated fatty acids;
• in the dispute about the role of alcohol in the origin of prostate cancer, there are compromise judgments - the responsibility of alcohol for the development of chronic pancreatitis, which predisposes to the development of a tumor;
• a large group of harmful chemical and physical factors increases the risk of developing a tumor with prolonged industrial and household contact;
• genetic predisposition - the presence of cancer in relatives;
• parasitic invasion (opisthorchiasis, clonorchiasis), nonspecific ulcerative colitis.

The following diseases predispose to cancer of the gallbladder and extrahepatic ducts:

• the leading factor in the development of such diseases as gallbladder cancer and, to some extent, extrahepatic duct tumors is long-term cholelithiasis. Apparently, frequent trauma to the mucosa and chronic inflammation are the trigger mechanism in epithelial dysplasia;
• Primary sclerosing cholangitis is combined with ductal neoplasms in approximately 14% of patients;
• adenomatous polyps, especially those with a diameter greater than 1 cm, are often subject to malignancy;
• chronic cholecystitis as a complication of typhoid-paratyphoid infection may be the background for the development of this disease;
• A certain significance is attached to biliary cirrhosis, congenital fibrosis and polycystic liver disease in the occurrence of Klatskin tumor.

The most common histological forms are adenocarcinoma and scirrhus.

Gallbladder Cancer: Symptoms

Gallbladder cancer has symptoms, especially in the early stages, which are generally characterized by the absence of specific signs. For quite a long time, in particular, except for signs of background diseases, there are no other manifestations. About 10% of patients have paraneoplastic Trousseau syndrome - migratory thrombophlebitis.

During the course of the disease of this group, pre-icteric and icteric periods of varying duration are noted. Early symptoms in the pre-icteric period are completely non-specific. Patients may complain of epigastric bloating, a feeling of heaviness in the right hypochondrium, nausea, bowel disturbances, general malaise, weakness, weight loss. The duration of the pre-icteric period is directly dependent on the localization of the pathological focus and proximity to the bile ducts. Thus, with neoplasms of the extrahepatic ducts, large duodenal papilla, head of the pancreas, this period is significantly shorter than with localization of the pathological focus in the body and tail of the pancreas.

The leading, and in some cases the first, but not the earliest, symptom complex is mechanical jaundice. It occurs due to the germination or compression of the common duct and the disruption of the outflow of bile into the duodenum. The icteric period is characterized by persistent and intense mechanical jaundice, an increase in the size of the liver (Courvoisier's symptom), the appearance of discolored feces and dark brown urine.

Mechanical jaundice is observed in 90-100% of cases with tumors of the extrahepatic ducts, in 50 to 90% of cases with neoplasms of the head of the pancreas, and in 50% of cases with pathology of the parapapillary zone of the duodenum. It is accompanied by endogenous intoxication syndrome, hepatorenal failure, inhibition of the coagulation system, decreased immunological status, metabolic disorders, inflammation of the ducts, etc.

Implantation metastasis in neoplasms of the biliopancreatoduodenal zone is not often observed and occurs through contact transfer of tumor cells along the peritoneum with the development of carcinomatosis and cancerous ascites.

As a result of the generalization of the tumor process, most patients come to an oncologist in advanced terminal stages and have no real chance of recovery.

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How to recognize gallbladder cancer?

Gallbladder cancer is difficult to diagnose. This is due to the fact that errors are often made at the diagnostic outpatient stage and most patients get to an oncologist when the chances of recovery remain minimal.

Diagnostic and tactical errors at the pre-hospital stage are often associated with low oncological literacy of first-contact doctors, their insufficient familiarity with this fatal pathology, difficulties in differential diagnosis, and other factors.

Gallbladder cancer, like other malignant neoplasms, should be diagnosed in a comprehensive and multi-stage manner. It is necessary to take into account the anamnesis data, the results of an objective examination, use routine and high-tech instrumental diagnostic methods and necessarily obtain morphological verification of the pathological process.

Gallbladder cancer has the following diagnostic stages:

1. primary diagnostics;
2. verification of the tumor process;
3. definition of staging;
4. characteristics of the functional capabilities of organs and systems.

Primary diagnostics

Of great importance at this diagnostic stage are anamnesis data indicating the presence of risk factors, precancerous diseases. It is necessary to study the dynamics of the pathological process before the patient is admitted to hospital: manifestations of the pre-icteric and icteric period, etc.

Laboratory methods

Among laboratory methods, the determination of tumor markers is widely used: CA-19-9, CEA, CA-50, etc.

The CA-19-9 marker is not entirely specific, but has an important prognostic value. The marker is almost always positive for tumors larger than 3 cm, and its level increases as the tumor process progresses.

Almost half of patients with gallbladder cancer have carcinoembryonic antigen CEA, which allows differentiation of benign tumors from malignant ones.

Blood tests reveal anemia, leukopenia, increased ESR, increased lipase and amylase, alkaline phosphatase, and trypsin inhibitors.

Instrumental diagnostics

This group of diagnostic methods is divided into non-invasive and invasive. The former include X-ray and ultrasound examination, computed tomography and diagnostics using nuclear magnetic resonance. Invasive methods include various types of endoscopic diagnostics, laparoscopy and morphological diagnostics.

X-ray diagnostics includes:

• X-ray examination of the stomach and duodenum. This routine method can reveal various organ deformations caused by compression or invasion by a neoplasm and impaired motility of the duodenum;
• Relaxation duodenography allows us to identify intestinal deformations, its displacement, and expansion of the “horseshoe”;
• In some cases, irrigoscopy can detect compression or invasion of the transverse colon.

Routine ultrasonography allows to exclude cholelithiasis and to establish cancer of the gallbladder. The examination allows to reveal an increase in the size of the gland and its head, blurring of contours, the condition of the parenchyma of the gland and the presence of heterogeneous echostructures. Symptoms of hepatic hypertension can be determined: expansion of intra- and extrahepatic ducts.

Computer tomography is more accurate and stable than ultrasound, reveals gallbladder cancer, the state of the hepatobiliary zone, and allows to correctly determine the stage of the disease. In 90% of patients, an indirect sign is determined - expansion of the ducts with mechanical jaundice.

The methods of nuclear magnetic resonance and positron emission tomography (PET) are still difficult to access for practical institutions, but they allow detecting small-sized gallbladder cancer, local vascular invasion, and conducting differential diagnostics.

For the purpose of diagnosing neoplasms of extrahepatic ducts, high-tech and informative X-ray endoscopic and X-ray surgical techniques are currently used:

• Retrograde endoscopic cholangiopancreatoscopy and cholangiopancreatography allow visual determination of gallbladder cancer and its localization. The main advantage of the method is the possibility of morphological verification of the neoplasm of the large duodenal papilla and extrahepatic ducts;
• Percutaneous transhepatic cholangiography (PTC) is not only a diagnostic but also a therapeutic measure: it establishes the level and degree of duct occlusion and, when draining them, eliminates hypertension and relieves inflammatory edema in the area of the tumor stricture;
• Endoscopic ultrasound scanning allows for accurate topical diagnostics of the tumor and determination of the condition of regional lymph nodes.

Gallbladder cancer is difficult to confirm morphologically and in some cases is an insoluble problem at the preoperative stage.

With the introduction of high-tech methods, it has now become possible to obtain material for morphological examination by percutaneous biopsy of pancreatic neoplasms and lymph nodes under the control of transabdominal and endoscopic ultrasound examination. Retrograde endoscopic cholangiopancreatoscopy allows for biopsy of neoplasms of extrahepatic ducts.

These methods have not yet become widespread in the general medical network and are used in specialized hospitals.

Determination of the stage of the disease

The objectives of this stage of diagnostics, as with other tumor localizations, are to identify the local spread of the pathological process and the presence of metastasis to distant organs.

To solve the first problem, such informative and technological methods as simple and endoscopic ultrasound scanning, X-ray computed tomography are used in practice, which allow obtaining a spatial image, its relationship with surrounding tissues, large vessels and nerve trunks; they provide information on the state of regional lymph nodes and allow for targeted puncture biopsy.

In recognizing distant organ metastases, chest X-ray, ultrasound and CT of the lungs and liver, and radioisotope diagnostics are of significant importance. Bone scintigraphy, if indicated, allows for the detection of intraosseous metastases much earlier than X-ray.

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Determination of the functional capabilities of organs and systems

Under the influence of the development of a malignant neoplasm in the patient's body, various disorders of compensatory mechanisms, functional abilities of the main life support systems, and immunological status arise. The task of this stage is to identify and correct these disorders, especially mechanical jaundice.

As a result of the examination, a detailed diagnosis is established with characteristics of the primary tumor and the prevalence of the tumor process.

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How is gallbladder cancer treated?

Treatment of patients with gallbladder cancer is a complex, multi-stage, high-tech process. Treatment is carried out for the following purposes:

• radical treatment involves, if possible, complete removal of the neoplasm and existing satellite microfoci, and prevention of the occurrence of metastases and relapses;
• The goal of palliative and symptomatic treatment is to eliminate such serious complications of the tumor as mechanical jaundice, cholangitis; to improve the quality and duration of life.

The choice of treatment method for the pancreatoduodenal zone is significantly influenced by numerous factors:

• clinical, biological and morphological features of the neoplasm;
• localization of the tumor in a particular organ and the degree of its malignancy;
• the degree of sensitivity of the tumor to various types of treatment;
• the severity of the patient's condition, caused by complications of the disease and breakdowns in the homeostasis system, etc.

When drawing up a treatment plan for a patient with neoplasms of the biliopancreatoduodenal zone, the following rules should be strictly followed:

• upon completion of the diagnostic stage, the final decision on treatment tactics should be made by a council consisting of a surgical oncologist, a radiologist and a chemotherapist;
• treatment most often must be multi-stage and multi-component;
• high-tech treatment using modern methods must be carried out at a specialized medical institution;
• The use of fairly aggressive and stressful methods in treatment dictates the need to solve an important problem: treatment should not be more severe than the disease and should contribute to improving the quality of life.

Selecting the optimal and individual treatment option is extremely difficult, since a large percentage of patients are admitted to hospital in an advanced metastatic stage.

The basis of treatment of patients with tumors of the pancreas and ducts, as with other neoplasms, is the combined, consistent use of local, locoregional and systemic methods of influence.

A certain optimism in improving the treatment results for patients with this complex and sometimes fatal pathology is caused by the use of high-tech methods:

• percutaneous transhepatic endobiliary drainage (PTEBD);
• Method of intraductal contact radiation therapy with Ir-191 threads.

The main method of treating patients in this group remains surgical in various forms: from palliative, aimed mainly at bile drainage, to extended combined operations.

Despite the high mortality rates and unsatisfactory long-term results, palliative bile drainage operations have a right to exist in severe patient conditions and as the first stage before radical surgical intervention.

In case of tumors of the head of the pancreas, large duodenal papilla and terminal section of the common bile duct, various biliodigestive anastomoses are considered palliative interventions. Methods of "bloodless bile drainage" are also used: percutaneous transhepatic recanalization of the hepaticocholedochus with endobiliary prosthetics or stenting, external or external-internal drainage of ducts.

Surgical intervention should always be preceded by detoxification therapy, and in cases of severe liver failure, extracorporeal detoxification methods are used: hemo- and lymphosorption, intravascular ultraviolet and laser irradiation of blood, etc.

In case of neoplasms of the proximal section of the common bile duct (Klatskin), the volume of the operation is considered radical: resection of the hepaticocholedoch with resection of the square lobe or hemihepatectomy. Such operations are performed only in specialized departments by highly qualified surgeons. However, even they do not give encouraging results yet: the percentage of postoperative complications is very high (up to 56%), and the five-year survival rate barely reaches 17%.

For tumors of the large duodenal papilla and the proximal common bile duct, the radical method is considered to be pancreatoduodenal resection followed by the use of radiation therapy.

There are still debates about the effectiveness of using radiation and chemotherapy in the complex treatment of neoplasms of this localization. Many oncologists consider chemotherapy to be ineffective.

From a practical standpoint, various radiation sources are used: remote gamma therapy, bremsstrahlung, fast electrons.

Irradiation is used before surgery (extremely rarely), intraoperatively and after surgery.

Intraoperative irradiation is performed at a dose of 20-25 Gy and as a component of complex treatment it can be combined with external irradiation, which improves the results of local disease control: the median survival is 12 months.

The following advanced technologies are currently used as a radiation component in the postoperative period for tumors of the extrahepatic ducts:

• intraluminal radiation therapy of tumor strictures of the common duct and anastomosis zones after resection of the common hepatic duct;
• Intraductal contact radiation therapy with Ir-191 threads.

Such methods of treating patients with locally advanced cancer, carried out using high total focal doses of radiation, are an effective treatment measure leading to an improvement in the quality of life of patients and an increase in its duration.

Scientists are conducting research to study the results of using neoadjuvant and adjuvant chemotherapy in the treatment of neoplasms of the pancreatoduodenal zone, but so far they are unconvincing.

Old, proven drugs such as fluorouracil, doxorubicin, ifosfamide, and nitrosoureas are used.

Attempts are being made to deliver drugs to the tumor site using ferromagnets (microcapsules) in a controlled magnetic field and the use of monoclonal antibodies in the complex treatment of tumors in this location.

What is the prognosis for gallbladder cancer?

Gallbladder cancer has an extremely unfavorable prognosis and is primarily due to the advanced stage of the tumor process already at the first visit of the patient to an oncologist.

Surgical treatment is radical in only 5-10% of cases, gallbladder cancer recurs in 50% of patients, and distant metastases develop in 90-95% of patients who have undergone pancreatoduodenal resection within the first year. Patients most often die from rapidly increasing tumor intoxication, cachexia, mechanical jaundice and other serious complications.

Even the use of combined and complex treatments slightly improves long-term results: five-year survival of patients with gallbladder cancer is about 5%, most patients die within 1.0-1.5 years after surgery. Even after radical surgeries, only 10% of patients live for 5 years.

Improving the treatment results for this complex pathology is primarily associated with the development of early diagnostic methods and components of complex high-tech treatment.