Cancer of the gallbladder

Among all malignant neoplasms of internal organs, gallbladder cancer, 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 caused by them, as well as the similarity of pathogenetic mechanisms, clinical manifestations, complications and methods of treatment.

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

Cancer of the gallbladder occupies the 5th-6th place in the structure of malignant neoplasms of the gastrointestinal tract, the proportion in the structure of all malignant tumors does not exceed 0.6%.

More often the cancer of the gallbladder occurs in women over 40 years old on the background of cholelithiasis.

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

[1], [2], [3],

What causes gallbladder cancer?

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

What causes gallbladder cancer is still unknown. Currently, it is difficult to distinguish the etiologic factor in each patient, so when searching for people at increased risk of developing the neoplastic process, those conditions that most often contribute to the realization of the oncogene are taken into account. These include the following risk parameters:

• unambiguous judgments about the role of food products in the emergence of neoplasm, in particular the use of animal protein and meat, as well as the content of saturated and unsaturated fatty acids;
• in the debate 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, predisposing to the development of the tumor;
• a large group of harmful chemical and physical factors increases the risk of developing a tumor with prolonged production and household contact;
• genetic predisposition - the presence of cancer in relatives;
• parasitic infestation (opisthorchiasis, clonorchosis), ulcerative colitis.

Cancers of the gallbladder and extrahepatic ducts have the following predisposing diseases:

• the leading factor in the onset of such a disease as gallbladder cancer and to some extent the tumor of the extrahepatic ducts is the long-existing cholelithiasis. Apparently, frequent mucosal trauma and chronic inflammation are the trigger mechanism in epithelial dysplasia;
• primary sclerosing cholangitis combined with neoplasm of the ducts in approximately 14% of patients;
• adenomatous polyps, especially those larger than 1 cm in diameter, are often malignant;
• chronic cholecystitis with complication of typhoid paratyphoid infection can be a background for the development of this disease;
• certain significance is attached to biliary cirrhosis, congenital fibrosis and polycystosis of the liver in the onset of the Klatskin tumor.

The most frequent histological forms are adenocarcinoma and scirrus.

Cancer of the gallbladder: symptoms

Cancer of the gallbladder has symptoms, especially in the early stages, which are generally characterized by the absence of specific signs. Quite a long time, in particular, except for signs of background diseases, there are no other manifestations. Approximately 10% of patients experience paraneoplastic Tussaud's syndrome - migrating thrombophlebitis.

In the course of the disease of this group, different doses are noted for the period of anicteric and icteric periods. Early symptoms in the pre-egg period are completely nonspecific. Patients may complain of epigastric swelling, a feeling of heaviness in the right hypochondrium, nausea, stool discomfort, general malaise, weakness, weight loss. The duration of the pre-egg period is directly dependent on the localization of the pathological focus and proximity to the bile ducts. Thus, with neoplasms of extrahepatic ducts, a large duodenal papilla, the head of the pancreas, this period is much shorter than when the pathological focus in the body and tail of the pancreas is localized.

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

Mechanical jaundice is noted in tumors of the extrahepatic ducts in 90-100% of cases, with pancreatic head malignancy - from 50 to 90% of cases, with pathology of the parapapillary zone of the duodenum - in 50% of cases. It is accompanied by a syndrome of endogenous intoxication, hepatic renal failure, oppression of the coagulation system, a decrease in the immunological status, a metabolic disorder, an inflammation of the ducts, etc.

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

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

[4], [5],

How to recognize gallbladder cancer?

The cancer of the gallbladder is difficult to diagnose. This is due to the fact that at the diagnostic polyclinic stage mistakes are often made and most patients get to the oncologist when the chances of recovery remain minimal.

Diagnostic and tactical errors at the prehospital stage are often associated with low oncological literacy of first contact physicians, inadequate knowledge of them with this fatal pathology, difficulties in differential diagnosis, and other factors.

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

The cancer of the gallbladder has the following diagnostic steps:

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

Primary diagnosis

Of great importance at this diagnostic stage are the history data, indicating the presence of risk factors, precancerous diseases. It is necessary to study the dynamics of the course of the pathological process prior to admission of the patient to the hospital: the manifestations of the jaundice and icteric period, etc.

Laboratory methods

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

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

Almost half of the patients with gall bladder cancer have carcinoembryonic CEA antigen, which allows to differentiate benign neoplasms from malignant ones.

The blood test determines anemia, leukopenia, accelerated ESR, increased lipase and amylase, alkaline phosphatase, trypsin inhibitors.

Instrumental diagnostics

This group of diagnostic methods is divided into non-invasive and invasive. The first include X-ray and ultrasound, 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 of the stomach and duodenum. With this routine method, various deformities of the organs can be detected due to the compression or germination of their neoplasm and the violation of the motility of the duodenum;
• relaxation duodenography makes it possible to detect bowel deformations, its displacement, the expansion of the "horseshoe";
• Irrigoscopy in some cases allows the establishment of compression or germination of the transverse colon.

Routine smile smile making allows to reject a cholelithiasis and to establish a cancer of a cholic bubble. In the study, it is possible to detect an increase in the size of the gland and its head, the fuzziness of the contours, the condition of the parenchyma of the gland, and the presence of heterogeneous echostructures. Symptoms of hepatic hypertension may be defined: enlargement of intra- and extrahepatic ducts.

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

The method of nuclear magnetic resonance and positron emission tomography (PET) is still difficult for practical institutions, but they can detect small-sized gallbladder cancer, local invasion of vessels, and carry out differential diagnostics.

In order to diagnose neoplasms of extrahepatic ducts, high-tech and informative X-ray endoscopic and X-ray surgical techniques are currently used:

• retrograde endoscopic cholangiopancoscopy and cholangiopancreatography can visually determine the cancer of the gallbladder and its localization. The main advantage of the method is the possibility of morphological verification of the neoplasm of the large duodenal nipple and extrahepatic ducts;
• percutaneous transhepatic cholangiography (CHCHKH) is not only diagnostic but also therapeutic: it establishes the level and degree of occlusion of the ducts and drains them to eliminate hypertension, relieves inflammatory edema in the zone of tumor stricture;
• endoscopic ultrasound scanning allows an accurate topical diagnosis of the tumor and the state of regional lymph nodes.

Cancer of the gallbladder is difficult to confirm morphologically and in some cases is an unsolvable task at the preoperative stage.

With the introduction of high-tech techniques, it has now become possible to obtain material for morphological investigation by percutaneous biopsy of the pancreas and lymph nodes under the control of transabdominal and endoscopic ultrasound. Retrograde endoscopic cholangiopancoscopy allows biopsy of neoplasm of extrahepatic ducts.

These methods are not yet widely used in the general medical network and are used in specialized hospitals.

Determination of the stage

The tasks of this stage of diagnosis, as well as in other tumor localizations, are to identify the local spread of the pathological process and the presence of metastasis in distant organs.

To solve the first problem in practice, use such informative and technological methods as simple and endoscopic ultrasound scanning, X-ray computed tomography, which allow to obtain 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.

Radiography of the lungs, ultrasound and CT of lungs and liver, radioisotope diagnostics are of great importance in the recognition of distant organ metastases. Scintigraphy of the bones of the skeleton in the presence of indications allows us to establish the presence of intraosteal metastases much earlier than the radiography.

[6], [7], [8], [9], [10]

Determination of the functional abilities of organs and systems

Under the influence of development of malignant neoplasm in the patient's body there are various violations of compensatory mechanisms, functional abilities of the basic life support systems, immunological status. 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 the characteristics of the primary tumor and the prevalence of the tumor process.

[11], [12]

How is gallbladder cancer treated?

The treatment of patients with gallbladder cancer is a complex multi-stage and high-tech process. Treatment is conducted for the following purposes:

• when radical treatment is provided, if possible, complete removal of the neoplasm and existing satellite microfrages, the prevention of metastases and relapses;
• the goal of palliative and symptomatic treatment is the elimination of such formidable complications of the tumor as mechanical jaundice, cholangitis; improvement of quality and life expectancy.

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

• Clinico-biological and morphological features of the neoplasm;
• tumor localization in this or that organ and degree of its malignancy;
• degree of tumor sensitivity to different types of treatment;
• 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 neoplasm of the bi-pancreatoduodenal zone, the following rules should be strictly adhered to:

• At the end of the diagnostic stage, the final decision on medical tactics should be taken by a consultation consisting of an oncologist, a radiologist and a chemotherapist;
• treatment should often be multi-stage and multicomponent;
• high-tech treatment with the use of modern techniques should be carried out on the basis of a specialized medical institution;
• the use of aggressive enough and stressful methods in treatment dictates the need to solve an important problem: treatment should not be more serious than the disease and should improve the quality of life.

The choice of the optimal and individual treatment option is extremely difficult, since a large percentage of patients enter the hospital in the advanced metastatic stage.

The treatment of patients with pancreatic and ductal tumors, as with other tumors, is combined, consistent use of local, locoregional and systemic methods of exposure.

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

• percutaneous transhepatic X-ray endotracheal drainage (CHSRBD);
• a technique of intra-current contact radiotherapy with Ir-191 filaments.

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

Despite the high rates of mortality, as well as unsatisfactory long-term results, palliative biliary excretion has the right to exist in the severe condition of the patient and as the first stage before radical surgical intervention.

For tumors of the head of the pancreas, the large duodenal nipple, and the terminal section of the choledochus, palliative interventions include various biliodigestive anastomoses. The methods of "bloodless bile excretion" are also used: percutaneous transhepatic recanalization of hepatitis choledochus with endobiliary prosthetics or stenting, external or external-internal drainage of ducts.

Operative intervention should always be preceded by detoxification therapy, and in case of severe hepatic insufficiency, extracorporeal detoxification methods are used: hemo- and lymphosorption, intravascular ultraviolet and laser irradiation of blood, etc.

In neoplasms of the proximal choledocha (Klatskin), the volume of surgery is considered to be radical: resection of hepatitis choledochus with resection of a square fraction or hemihepatectomy. Such operations are performed only in specialized departments by highly qualified surgeons. However, they do not yet give encouraging results: the percentage of postoperative complications is high (up to 56%), and the five-year survival rate barely reaches 17%.

In tumors of the large duodenal nipple and proximal choledocha, a pancreatoduodenal resection using radiotherapy is considered a radical method.

There are still disputes about the effectiveness of radiotherapy and chemotherapy in the complex treatment of neoplasms of this localization. Many oncologists consider chemotherapy ineffective.

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

Irradiation is used before surgery (very 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: median survival is 12 months.

As a radiation component in the postoperative period, the following advanced technologies are used for tumors of extrahepatic ducts:

• Intraluminal radiation therapy of tumor strictures of the common duct and anastomosis zones after resection of hepatitis choledocha;
• intra-flow contact radiation therapy with Ir-191 filaments.

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

Scientists are conducting studies on the results of the use of neoadjuvant and adjuvant chemotherapy in the treatment of neoplasms of the pancreatoduodenal zone, but so far they are unconvincing.

Use old tested drugs, such as fluorouracil, doxorubicin, ifosfamide, nitrosoureas.

Attempts are made to add drugs to the tumor focus with the help of ferromagnets (microcapsules) in a controlled magnetic field and the use of monoclonal antibodies in the complex treatment of tumors of this localization.

What prognosis does gallbladder cancer have?

Cancer of the gallbladder has an extremely unfavorable prognosis and is due primarily to the neglect of the tumor process already at the first referral of the patient to the oncologist.

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

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

Improving the results of treatment of this complex pathology is primarily due to the development of methods for early diagnosis and components of complex high-tech treatment.