Hepatic cancer metastases

In the initial diagnostic of colorectal cancer and single hepatic metastases, we highly recommend active surgical treatment with simultaneous removal of the primary focus and metastases. This allows increasing the five-year survival rate up to 30-40% of all primarily operated patients.

Causes for appearance of hepatic metastases

The liver is one of the most vascularized organs. Every minute, up to 30-40% of the entire blood volume passes through it, on average about 1.5 liters per minute. In this case, approximately 30–35% of the blood enter through hepatic arteries, and the remaining 70–75% through the portal vein from the intestine. After that, both these flows mix and return to the heart through the inferior vena cava.

Due to the special nature of its blood supply, the liver is a place for “entrapment” of tumor cells, which leads to the most frequent localization of hematogenous metastases of tumors therein, regardless of whether the primary tumor is drained by the portal vein system or by other veins of the greater circuit.

At the same time, half of the metastases come from primary tumors localized in the abdominal cavity and small pelvis and draining into the portal vein system. Thus, in case of a colorectal cancer, after radical resection of the affected intestine region without subsequent relapse in the primary operation area,  PET-CT shows single hepatic metastases in approximately 50% of cases.

For other gastrointestinal tumors, including cancer of the stomach, esophagus, pancreas, metastases are detected in approximately 40-50% of patients. With pulmonary, mammary cancer and melanoma, metastases are detected in approximately 30% of patients. Very rarely hepatic metastases occur with cancer of the mouth cavity, pharynx, prostate, urinary bladder. Quite rare are hepatic metastases with cancer of the uterus, ovaries, pharynx, mouth cavity, urinary bladder and kidneys.

It is important to note that approximately 2/3 of metastases histologically and immunohistochemically replicate the “maternal” tumor, and 1/3 morphologically differ from primary tumors by the degree of differentiation of tumor cells, which makes it difficult to establish the organ affiliation of the primary tumor.

Symptoms of hepatic cancer metastases

If a patient has single hepatic metastases, in most cases due to the high regenerative capacity of the liver they do not manifest themselves for a long time until they reach a diameter of 5-7 cm or begin to compress the biliary tract. In the presence of a primary tumor focus (before radical or cytoreductive surgery), the clinical symptoms of metastases are summarized with the symptoms of the primary neoplasm.

Speaking about hepatic metastases, the disease may manifest itself with the following signs. First of all, it is astheno-vegetative syndrome. The patient loses a good deal in body weight while maintaining a normal diet and appetite, complaining of constant fatigue and a feeling of weakness and being unrested at any time of the day. Performance gradually decreases.

Persistent acute paroxysmal or minor pains in the right side appear, sometimes accompanied by an unpleasant sensation of friction in the right hypochondrium. The patient complains of uncontrolled nausea and vomiting, bitter belching, diarrhea or constipation. The skin gets an ashy hue. All manifestations of this syndrome are due to functional impairment of the biliary and detoxifying liver functions, and, in principle, they are reversible in case of elimination of the primary factor, the hepatic cancer metastasis.

The biliary tract obstruction syndrome develops due to compression by the tumor mass of the major bile ducts, first of all, the common and lobar intrahepatic ones. The patient constantly complains about arching pains in the right hypochondrium. The patient also starts to be bothered by itching, the skin and scleras become yellowish. Spontaneous bouts of fever occur. Urine color becomes dark (beer-like).

The inferior vena cava compression syndrome is accompanied by persistent edemas of the lower extremities that remain unchanged during the day, accompanied by accumulation of fluid in the abdominal cavity. The pain becomes diffuse throughout the abdomen.

Gradually, the severity of the astheno-vegetative syndrome together with the biliary tract and inferior vena cava compression syndrome increases. The hepatic function decompensation leads to a weight loss up to cachexia, the extreme degree of exhaustion, while there is a deterioration in appetite up to a complete food rejection.

The portal hypertension syndrome with compression of the portal vein adds to compression of the biliary tract, and as a result, obstructive jaundice develops. Consequently, by the law of communicating vessels there occurs an expansion of veins of the esophagus, rectum and anterior abdominal wall (cirsomphalos), which leads to episodic hemorrhages from the dilated veins. A small ascites enlarges, reaching a maximum of 20-25 liters according to our clinical data.

The most dangerous condition develops closer to the end of the disease, manifesting itself in persistent vomiting lasting up to a day, especially with scarlet blood, black excrements, and a great abdomen enlargement. As a rule, there is gastric or intestinal bleeding that requires urgent surgical assistance.

Diagnostics of hepatic cancer metastases

In most cases, hepatic cancer metastases are diagnosed during some other examination (for example, in a planned cholecystectomy), less frequently during the examination regarding the lesion nature clarification with the primary cancer of other localization.

As a rule, study includes non-invasive and invasive examination methods. Among the non-invasive ones, the simplest and most accessible is liver ultrasound which mainly performs the screening function. However, its resolution limits make it impossible to detect metastases less than 0.4-0.5 cm in diameter.

Such visualization methods as PET-CT, CT or MRI scan allow to assess their size, number, location, growth pattern, to detect suppuration, disintegration and involvement of neighboring tissues and organs in the tumor process.

However, the diagnostics of micrometastases in the hepatic area is based on portography with contrast enhancement, which allows a detailed study of the state of blood flow in the portal vessels. Micrometastases themselves are detected on portograms on the basis of depletion of the vascular pattern in the area of metastatic lesions. With their help, damage to the vascular bed can be observed, while the procedure is supervised on the CT monitor.

Invasive diagnostics of hepatic cancer metastases involves a liver biopsy, including using a needle (fine-needle aspiration biopsy) or a special instrument called trephine (core needle biopsy, trephine biopsy).

The biomaterial is sent to a specialized laboratory for histological and immunohistochemical studies. On the one hand, 2/3 of metastases coincide in their histological portrait with the maternal tumor, however, 1/3 do not.

All of the above diagnostic methods are available for patients of the Clinic Medicine 24/7.

How are hepatic metastases treated?

The tactics of treating hepatic cancer metastases is determined by the number of metastases (single or multiple), their localization in the region of the liver edge or gates, and the histological type of cancer.

Basically, all the main methods of treating hepatic cancer metastases include surgical, chemotherapeutic and radiation options, as well as chemoembolization. The Clinic Medicine 24/7 performs all major types of liver operations, including lobar, segmental and atypical resections. Moreover, Professor A. Severtsev is one of the few in Russia who performs the so-called liver autotransplantations (“Pichlmayr’s operation”), with the removal of liver metastases “on the second table”.

In addition to exclusive liver surgeries, our experts routinely perform modern minimally invasive interventions on the liver including percutaneous transhepatic radiofrequency ablation (RFA), as well as liver RFA during laparoscopic and open laparotomic operations.

Treatment of hepatic metastases has its difficulties. Thus, about 1/3 of all hepatic metastases are insensitive to chemotherapy drugs used to eliminate the primary tumor. Therefore, to ensure effective chemotherapy of metastatic liver cancer it is necessary for most patients to combine chemotherapy and targeted drugs.

Moreover, in many cases of metastatic liver cancer a systemic chemotherapy proves ineffective, and the chemotherapy agent has to be administered through the hepatic artery. Our clinic applies for the purposes of regional chemotherapy for hepatic cancer metastases  implantable venous and arterial port systems with subsequent regional infusion of chemotherapy drugs. Drugs with proven efficacy have been registered in Russia for targeted treatment of hepatic cancer metastases.

Chemoembolization of hepatic metastases is used to treat single and large metastases located near major neurovascular bundles when surgical resection is difficult or impossible. Chemoembolization is performed using microspheres filled with a chemotherapy drug. Microspheres limit blood flow in the metastatic node, while the chemotherapy drug itself is released during a long period of time and leads to necrosis of tumor tissue.

RFA of hepatic metastases can be used repeatedly for cancer relapses. Most often it is included in the integrated therapy.

Radiation therapy is almost ineffective in case of hepatic metastases, since it does not affect the survival rate of patients and their life expectancy. It only allows to occasionally reduce the intensity of pain.

The main thing that our patients need to know is the ability to achieve a positive treatment result for any hepatic metastasis type.

What are the prospects with hepatic cancer metastases?

The most common questions asked by relatives of patients entering the Clinic Medicine 24/7 with hepatic metastases are “does it make sense to treat metastases at the fourth stage of cancer”, “should the patient be operated”, “what is the life prognosis and treatment outcome”? The treatment outcome is determined by the genetic portrait of the tumor, the degree of differentiation of the tumor, and the location of the primary tumor.

In general, it is important to know that after the initial detection of hepatic metastases, patients live on average for 6-18 months. Slightly higher is life expectancy for patients with primary colon cancer and hepatic metastases. With an integrated patient follow-up, radical or cytoreductive interventions, patients can live up to 2.5 years. If a PET-CT or a CT scan reveals metastases in bones or brain, the prognosis worsens dramatically.

Our oncologists and surgeons at the Clinic Medicine 24/7 have substantial experience in integrated treatment of hepatic metastases and primary tumors. Therefore, we can in many cases guarantee a significant improvement in the quality of life, and in some cases a significant extension of it. The greatest effect is achieved with highly differentiated metastases of highly differentiated adenocarcinoma of colon cancer. The prolongation of life as a result of treatment amounts for such patients to about 3-5 years. It is important to combine this intervention with cytoreductive surgery to remove the primary tumor focus.

If hepatic metastases are caused by primary cancer of the lung, pancreas, stomach and other organs, then resection of hepatic metastases is not so critical for determining the patients’ life expectancy. However, an economical resection, single-node RFA, chemoembolization reduce the toxic load on the liver and allow primary cancer chemotherapy.

If a checkup examination reveals multiple foci in the liver and lymph nodes, then the prognosis is much worse, being generally negative. In most of these cases, it is impossible to help radically, but it is possible to preserve the quality of life of patients by integrated blood purification procedures (plasmapheresis and hemosorption).

What are complications on the background of  combined treatment of hepatic metastases?

Against the background of repeated metastasis of the focus or hepatic relapse of the primary cancer, the expanding tumor tissue compresses the intrahepatic bile ducts, the portal vein, and the inferior vena cava. As a result, the existing signs of hepatic jaundice are complemented by obstructive jaundice, which leads to brain damage. The negative factor of obstructive jaundice is the impossibility of continuing chemotherapy and surgery.

In this case, a surgical restoration of the bile duct patency is performed by a temporary scheme using percutaneous transhepatic stenting, or by a permanent scheme using retrograde stenting of the common bile duct under endoscopic control. In the first case, bile flows outside into the bile receptacle. In the second case, bile enters the intestinal lumen.

Percutaneous transhepatic stenting is performed in an X-ray operating room under C-arm control. The interventions themselves are performed by X-ray endovascular surgeons with extensive experience of work in Russian public X-ray surgery centers.

Retrograde endoscopic stenting is also performed in an X-ray operating room with simultaneous C-arm and endoscopic control. The interventions themselves are performed by endoscopic physicians who have surgical skills and have been trained in various methods of biliary tract stenting.

What happens to the liver after removal of metastases?

When cancer metastases are removed by a non-invasive method using chemoembolization, radiofrequency ablation or radioembolization, a zone of necrosis is formed followed by its replacement with a cicatrix. This process usually takes from 2 to 6 months. The cicatrix is sometimes extensive and has a form of a dense cord or a node up to 2-4 cm in diameter. It can compress the internal bile ducts.

When hepatic metastases are removed non-invasively using a surgical method, the cicatrix is generally thread-like. Full restoration of the liver size and structure after large resections is observed after 3-6 months. In a healthy person, the liver can recover its full volume from the remnant after surgery amounting to 20% of the original.

In the case of massive resections in cancer patients with reduced regenerative capacity, recovery occurs within 6–8 months with the stump limit of 30% of the original liver size.

Where to treat hepatic cancer metastases: abroad or in Russia?

The diagnosis of stage 4 cancer is made already in the presence of a single hepatic metastasis. For almost every patient, such a diagnosis of “cancer with hepatic metastases” sounds like a death sentence. Having received it, many Russian patients refuse any treatment and stop fighting. Very few choose to fight on and go abroad.

In fact, in Russia, in Moscow, specifically in the Clinic Medicine 24/7, all modern technologies and drugs for the treatment of cancer metastases of any origin are available. We believe that the patient can always be helped, even if cannot be cured radically. That is why we undertake the treatment of patients with cancer at any stage. Our experts have amassed many years of experience in managing palliative patients with various stages of cancers of almost any localization, including those previously treated abroad, in Germany, Israel, Switzerland and the USA.

Questions most frequently asked by patients with hepatic metastases

Our expert in this area:

Alexei Nikolaevich Severtsev, Surgeon, Professor, Doctor of Medicine

Is treatment indicated in my particular case?

Just send me, Alexei Nikolaevich Severtsev, the results of your latest PET-CT, MRI, CT as a link to the Google or Yandex cloud archive. Describe all your problems in the cover letter.

How will the oncologist surgeon consultation take place?

In principle, the preliminary consultation is devoted to establishing the presence of the primary focus or its recurrence, the mutual location of metastases, and the prospects for conservative and surgical treatment.

One of our know-hows in determining the possibility of achieving a result after surgery in patients with hepatic cancer metastases is the combined performance of high-resolution CT and MRI in one day. The joint implementation of both examinations gives the oncologist surgeon a complete picture of the  pathological changes in the liver, and grounds to make an informed choice of the treatment scheme.

Reference list:

1. Plechev V. V., Mufazalov F. F., Shestakov A. I., Ishmetov V. Sh., Loginov M. O., Utenskaya I. D. Efficacy of treatment by chemoembolization in hepatocellular carcinoma and distant metastases into the liver (In Russian) // Bashkortostan Medical Journal. 2012. No. 1.
2. Zakharchenko Alexander Alexandrovich, Kochetova Lyudmila Victorovna. Options for the combined treatment of patients with hepatic metastases of colorectal cancer (In Russian) // Kazan Medical Journal. 2009. No. 2.
3. Aksel Е.М., Davydov М.I., Ushakova Т.I. Malignant neoplasms of the gastrointestinal tract: key statistics and trends (In Russian) // Journal of Modern Oncology. 2001. Vol. 3, No. 4. Pp. 141-145.
4. Patyutko Yu.I., Sagaydak I.V., Pylev A.L. Surgical and combined treatment for multiple and bilobar metastatic liver damage (In Russian) // Russian Journal of Surgery. 2005. No. 6. Pp.15-19.

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