Cost of liver cancer surgery In India

Surgery is among the very good treatment option in early stage liver cancer treatment. There are different types of liver cancer surgery to be performed and is decided by the specialist liver cancer surgeon. Type of surgery to be performed depends upon stage of the disease, spread of the disease to other parts and patient health condition. Along with the tumor surgeon also removes part of tissues surrounding tumor cells. It is likely to be the most successful disease-directed treatment, particularly for patients with good liver function and tumors that can be safely removed from a limited portion of the liver. Surgery may not be an option if the tumor takes up too much of the liver, the liver is too damaged, the tumor has spread outside the liver, or the patient has other serious illnesses. A surgical oncologist is a doctor who specializes in treating cancer using surgery. A hepatobiliary surgeon also has specialized training in surgery on the liver and pancreas. Sometimes, liver transplant surgeons are involved in these operations. Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have.

Patients eligible for liver cancer surgery

our specialist will only consider surgery if the cancer is contained in one area of your liver and has not spread to any other part of your body. This generally means stage 0 or stage A from the BCLC staging system. An operation would not cure the cancer if it has already spread. Unfortunately surgery is not possible for many people with primary liver cancer.

You have a series of blood tests to find out how well your liver is working before your doctor decides if surgery is an option for you. As the liver is such a vital organ, they need to know that the part of your liver left after your operation will work well enough to keep you healthy.

Types of liver cancer surgery

Partial hepatectomy

Partial hepatectomy is surgery to remove part of the liver. Only people with good liver function who are healthy enough for surgery and who have a single tumor that has not grown into blood vessels can have this operation.

Imaging tests, such as CT or MRI with angiography are done first to see if the cancer can be removed completely. Still, sometimes during surgery the cancer is found to be too large or has spread too far to be removed, and the surgery that has been planned cannot be done.

Most patients with liver cancer in the United States also have cirrhosis. In someone with severe cirrhosis, removing even a small amount of liver tissue at the edges of a cancer might not leave enough liver behind to perform important functions.

People with cirrhosis are typically eligible for surgery if there is only one tumor (that has not grown into blood vessels) and they will still have a reasonable amount (at least 30%) of liver function left once the tumor is removed. Doctors often assess this function by assigning a Child-Pugh score, which is a measure of cirrhosis based on certain lab tests and symptoms.

Patients in Child-Pugh class A are most likely to have enough liver function to have surgery. Patients in class B are less likely to be able to have surgery. Surgery is not typically an option for patients in class C.

Hepatectomy procedure

The surgical procedure is performed under general anesthesia and is quite lengthy, requiring three to four hours. The anesthetized patient is face-up and both arms are drawn away from the body. Surgeons often use a heating pad and wrappings around the arms and legs to reduce losses in body temperature during the surgery. The patient’s abdomen is opened by an incision across the upper abdomen and a midline-extension incision up to the xiphoid (the cartilage located at the bottom middle of the rib cage). The main steps of a partial hepatectomy then proceed as follows:

• Freeing the liver. The first task of the surgeon is to free the liver by cutting the long fibers that wrap it.
• Removal of segments. Once the surgeon has freed the liver, the removal of segments can start. The surgeon must avoid rupturing important blood vessels to avoid a hemorrage. Two different techniques can be used. The first has the surgeon make a superficial burn with an electric lancet on the surface of the liver to mark the junction between the sections marked for removal and the rest of the liver. He/she cuts out the section, and then tears towards the hepatic parenchyma. It is the difference in resistance between the parenchyma and the vessels that allows the surgeon to identify the presence of a vessel. At this point, he/she isolates the vessel by removing the surrounding connective tissue, and then clamps it. The surgeon can then cut the vessel, without any danger to the patient. The second technique involves identifying the large vessels feeding the segments to be removed. The surgeon operates first at the level of the veins to free and then clamp the vessels required. Finally, the surgeon can make incisions without worrying about cutting little vessels.

Risks & side effects of hepatectomy

Liver resection is a major, serious operation that should only be done by skilled and experienced surgeons. Because people with liver cancer usually have other liver problems besides the cancer, surgeons have to remove enough of the liver to try to get all of the cancer, but also leave enough behind for the liver to function.

• Bleeding: A lot of blood passes through the liver, and bleeding after surgery is a major concern. Also, the liver normally makes substances that help the blood clot. Damage to the liver (both before the surgery and during the surgery) can add to potential bleeding problems.
• Infection
• Complications from anesthesia
• Blood clots
• Pneumonia
• New liver cancer: Because the remaining liver still has the underlying disease that led to the cancer, sometimes a new liver cancer can develop afterward.

Liver transplant

When it is available, a liver transplant may be the best option for some people with liver cancer. Liver transplants can be an option for those with tumors that cannot be removed with surgery, either because of the location of the tumors or because the liver has too much disease for the patient to tolerate removing part of it. In general, a transplant is used to treat patients with small tumors (either 1 tumor smaller than 5 cm across or 2 to 3 tumors no larger than 3 cm) that have not grown into nearby blood vessels. It can also rarely be an option for patients with resectable cancers (cancers that can be removed completely). With a transplant, not only is the risk of a second new liver cancer greatly reduced, but the new liver will function normally.

According to the Organ Procurement and Transplantation Network, about 1,000 liver transplants were done in people with liver cancer in the United States in 2016, the last year for which numbers are available. Unfortunately, the opportunities for liver transplants are limited. Only about 8,400 livers are available for transplant each year, and most of these are used for patients with diseases other than liver cancer. Increasing awareness about the importance of organ donation is an essential public health goal that could make this treatment available to more patients with liver cancer and other serious liver diseases.

Most livers used for transplants come from people who have just died. But some patients receive part of a liver from a living donor (usually a close relative) for transplant. The liver can regenerate some of its lost function over time if part of it is removed. Still, the surgery does carry some risks for the donor. About 370 living donor liver transplants are done in the United States each year. Only a small number of them are for patients with liver cancer.

People needing a transplant must wait until a liver is available, which can take too long for some people with liver cancer. In many cases a person may get other treatments, such as embolization or ablation, while waiting for a liver transplant. Or doctors may suggest surgery or other treatments first and then a transplant if the cancer comes back.

Who are not right candidates for liver transplant ?

• Severe, irreversible medical illness that limits short-term life expectancy
• Severe pulmonary hypertension (mean pulmonary artery pressure greater than 50mmHg)
• Cancer that has spread outside of the liver
• Systemic or uncontrollable infection
• Active substance abuse (drugs and/or alcohol)
• Unacceptable risk for substance abuse (drugs and/or alcohol)
• History of non-compliance, or inability to adhere to a strict medical regimen
• Severe, uncontrolled psychiatric disease

Procedure for liver transplant

A liver transplant involves the removal of and preparation of the donor liver, removal of the diseased liver, and implantation of the new organ. The liver has several key connections that must be re-established for the new organ to receive blood flow and to drain bile from the liver. The structures that must be reconnected are the inferior vena cava, the portal vein, the hepatic artery, and the bile duct. The exact method of connecting these structures varies depending on specific donor and anatomy or recipient anatomic issues and, in some cases, the recipient disease.

For someone undergoing liver transplantation, the sequence of events in the operating room is as follows:

1. Incision
2. Evaluation of the abdomen for abnormalities that would preclude liver transplantation (for example: undiagnosed infection or malignancy)
3. Mobilization of the native liver (dissection of the liver attachments to the abdominal cavity)
4. Isolation of important structures (the inferior vena cava above, behind, and below the liver; the portal vein; the common bile duct; the hepatic artery)
5. Transection of the above mentioned structures and removal of the native, diseased liver.
6. Sewing in the new liver: First, venous blood flow is re-established by connecting the donor’s and the recipient’s inferior vena cava and portal veins. Next, arterial flow is re-established by sewing the donor’s and recipient’s hepatic arteries. Finally, biliary drainage is achieved by sewing the donor’s and recipient’s common bile ducts.
7. Ensuring adequate control of bleeding
8. Closure of the incision

Surgical Complications

As with any surgical procedure, complications related to the operation may occur, in addition to the many possible complications that may happen to any patient who is hospitalized. Some of the problems specific to liver transplantation that may be encountered include:

Primary non-function or poor function of the newly transplanted liver occurs in approximately 1-5% of new transplants. If the function of the liver does not improve sufficiently or quickly enough, the patient may urgently require a second transplant to survive.

• Hepatic artery thrombosis, or clotting of the hepatic artery (the blood vessel that brings oxygenated blood from the heart to the liver) occurs in 2-5% of all deceased donor transplants. The risk is doubled in patients who receive a living donor transplant. The liver cells themselves typically do not suffer from losing blood flow from the hepatic artery because they are primarily nourished by blood by the portal blood flow. In contrast, the bile ducts depend strongly on the hepatic artery for nutrition and loss of that blood flow may lead to bile duct scarring and infection. If this occurs, then another transplant may be necessary.
• Portal vein thrombosis or clotting of the large vein that brings blood from the abdominal organs (the intestines, the pancreas, and the spleen – the organs that belong to the portal circulation) to the liver occurs infrequently. This complication may or may not require a second liver transplant.
• Biliary complications: In general, there are two types of biliary problems: leak or stricture. Biliary complications affect approximately 15% of all deceased donor transplants and up to 40% of all living donor transplants.
  • Biliary leak means that bile is leaking out of the bile duct and into the abdominal cavity. Most frequently, this  occurs where the donor and recipient bile ducts were sewn together. This is often treated by placing a stent, or plastic tube, across the connection through the stomach and small intestine and then allowing the connection to heal. In the case of living donor or split liver transplants, bile can also leak from the cut edge of the liver.  Typically, a drain is placed and left during the transplant operation along the cut edge to remove any bile that may leak. As long as the bile does not collect in the abdomen, the patient does not become ill. Leaks will often heal with time, but may require additional treatment procedures.
  • Biliary stricture means narrowing of the bile duct, resulting in relative or complete blockage of the bile flow and possible infection. Most frequently, the narrowing occurs at a single site, again where the donor and recipient ducts are sewn together. This narrowing can often be treated by dilating the narrowed area with a balloon and/or inserting a stent across the stricture. If these methods are unsuccessful, surgery is often done to create a new connection between the liver’s bile duct and a segment of intestine. Rarely, biliary strictures occur at multiple or innumerable sites throughout the biliary tree. This occurs most frequently because the biliary tree was poorly preserved during the period when the liver was not in either the donor or recipient circulation. Livers procured from cardiac death donors are at higher risk than those from brain dead donors. Alternatively, diffuse biliary strictures may occur if the biliary tree has inadequate blood supply because of an abnormality with the hepatic artery.
• Bleeding is a risk of any surgical procedure but a particular risk after liver transplantation because of the extensive nature of the surgery and because clotting requires factors made by the liver. Most transplant patients bleed a minor amount and may get additional transfusions after the operation. If bleeding is substantial or brisk, return to the operating room for control of bleeding is often necessary. In general, approximately 10% of transplant recipients will require a second operation for bleeding.
• Infection – Infections can occur during the healing of the wound created by any operation. Liver transplant recipients are also at risk for infections deep within the abdomen, particularly if there is a collection of blood or bile (from a bile leak). The immunosuppressive medications along with the history of liver failure increase the liver transplant recipient’s risk for developing an infection after transplantation.

Immunosuppression

The human body has developed a very sophisticated series of defenses against bacteria, viruses, and tumors. The machinery of the immune system has evolved over millions of years to identify and attack anything that is foreign or not “self.” Unfortunately, transplanted organs fall into the category of foreign, not self. A number of drugs are given to transplant recipients to dampen the responses of their immune system in an attempt to keep the organ safe and free of immunologic attack. If the immune system is not sufficiently weakened, then rejection – the process by which the immune system identifies, attacks, and injures the transplanted organ – ensues.

Commonly used drugs to prevent rejection by suppressing the immune system are listed below. They work through different mechanisms to weaken the immune system’s responses to stimuli and are associated with different side effects. As a result, these medications are frequently used in various combinations which increase the overall immunosuppressive effect while minimizing side effects.

• Corticosteroids (methylprednisolone is given intravenously; prednisone is given orally): Corticosteroids are a class of anti-inflammatory agents that inhibit production of cytokines, the signaling molecules produced by cells of the immune system to orchestrate and intensify the immune response. Corticosteroids therefore prevent activation of lymphocytes, the main soldiers of the immune response against transplanted organs. This is thought to prevent T-cell (a subset of lymphocytes) activation in a non-specific manner. Side effects of corticosteroids are broad and include hyperglycemia, hypertension, decreased bone density, and impaired wound healing,
• Calcineurin inhibitors (cyclosporine, tacrolimus): This class of drugs blocks the function of calcineurin, a molecule critical to a very important lymphocyte signaling pathway that triggers the production of multiple cytokines. These drugs, first developed approximately 20 years ago, revolutionized organ transplantation. They substantially reduced the incidence of rejection, improved the longevity of transplanted organs and thereby ushered in the contemporary era of transplantation and immunosuppression. Unfortunately, these drugs come with a significant side effect profile. The most serious toxicity, particularly with long-term use, is kidney injury. Calcineurin inhibitors also raise blood pressure, glucose levels, and cholesterol – and cause tremors and headaches.
• Mycophenolate mofetil (Cellcept®, Myfortic®): This drug is converted in the body to mycophenolic acid, which inhibits the ability of lymphocytes to replicate DNA, the genetic material essential to every cell. If lymphocytes cannot synthesize DNA, then they are unable to divide to generate additional cells. Mycophenolate mofetil, therefore, dampens the immune response by preventing proliferation of lymphocytes. The primary side effects of mycophenolate mofetil affect the intestinal system resulting in stomach upset and/or diarrhea. It can also depress bone marrow function and thereby, reduce blood levels of white cells (infection fighting cells), red cells (oxygen carrying cells), and platelets (clotting agents).
• mTOR inhibitors (sirolimus; everolimus): mTOR stands for mammalian Target Of Rapamycin. mTOR belongs to a family of enzymes known as kinases and is involved in checkpoint regulation of the cell cycle, DNA repair, and cell death. Inhibition of mTOR stops T cells from progressing through the various phases of the cell cycle, leading to cell cycle arrest. Thus, lymphocytes are not able to divide to amplify the immune response. Side effects of mTOR inhibitors include bone marrow depression, poor wound healing, and increased cholesterol levels.
• Antibodies that target the IL-2 receptor, a signaling molecule that amplifies the immune response (basiliximab, daclizumab): T cells, the agents of acute rejection, express increasing amounts of IL2-receptors when they are stimulated. The IL-2 receptor allows ongoing amplification of an immune response. Blockage of this receptor therefore dampens the immune response. These antibodies are most frequently used for a short time period beginning at the time of transplant to provide additional immunosuppression during this period of highest rejection risk. Immediate side effects include fever, rash, cytokine release syndrome, and anaphylaxis. They do appear to increase the risk of infections hen combined with other immunosuppressive medications.
• Antibodies that remove T cells from the circulation (Thymoglobulin®, OKT-3®): These agents are molecules that target different cells of the immune system, bind them, inactivate, and remove them. They can be used at the time of liver transplantation. but more often are used to treat severe rejection or rejection that does not respond to lesser treatment strategies. Immediate side effects of these medications range from fever and rash to cytokine release syndrome resulting in flash pulmonary edema and hypotension. These drugs may also result in increased incidence of PTLD and skin cancers (see below)
• investigational drugs – As our understanding of the immune system improves, researchers have identified new cells, molecules, and pathways that play a role in the body’s response to transplanted organs. Each discovery presents new opportunities in the form of new targets for drug development. Some of these medicines are currently being tested in clinical trials to determine if they are safe and effective for use in transplantation. Future generations of drugs will hopefully be more specific in preventing rejection without interfering significantly with the other functions of the immune system or causing non-immunologic side effects.

Rejection

Rejection is a term that is applied to organ dysfunction caused by the recipient’s immune system reaction to the transplanted organ. Injury to the liver is typically mediated by immune cells, T cells or T lymphocytes. Rejection typically causes no symptoms; patients do not feel any differently or notice anything. The first sign is usually abnormally elevated liver laboratory test results. When rejection is suspected, a liver biopsy is performed. Liver biopsies are easily done as a bedside procedure using a special needle that is introduced through the skin. The tissue is then analyzed and inspected under the microscope to determine the pattern of liver injury and also to look for the presence of immune cells.

Acute cellular rejection occurs in 25-50% of all liver transplant recipients within the first year after transplantation with the highest risk period within the first four to six weeks of transplantation. Once the diagnosis is made, treatment is fairly straightforward and generally very effective. The first line of treatment is high dose corticosteroids. The patient’s maintenance immunosuppression regimen is also escalated to prevent subsequent rejection. A small proportion of acute rejection episodes, approximately 10-20%, does not respond to corticosteroid treatment and are termed “steroid refractory,” requiring additional treatment.

The second line of rejection treatment is strong antibody preparations. In liver transplantation, unlike other organs, acute cellular rejection does not generally affect overall chances for graft survival. This is believed to be because the liver has the unique ability to regenerate when injured thereby restoring full liver function.

Chronic rejection occurs in 5% or less of all transplant recipients. The strongest risk factor for the development of chronic rejection is repeated episodes of acute rejection and/or refractory acute rejection. Liver biopsy shows loss of bile ducts and obliteration of small arteries. Chronic rejection, historically, has been difficult to reverse, often necessitating repeat liver transplantation. Today, with our large selection of immunosuppressive drugs, chronic rejection is more often reversible.

Recurrent Disease

Some of the processes that led to the failure of the patient’s own liver can damage the new liver and eventually destroy it. Perhaps the best example is hepatitis B infection. In the early 1990’s, patients who received liver transplants for hepatitis B infection had less than 50% five year survival. The vast majority of these patients suffered from very aggressive reinfection of the new liver by hepatitis B virus. During the 1990’s, however, several drugs and strategies to prevent re-infection and damage of the new liver were developed and instituted widely by transplant centers. These approaches have been highly successful such that recurrent disease is no longer a problem. Hepatitis B, once considered a contra-indication to transplantation, is now associated with excellent outcomes, superior to many of the other indications for liver transplantation.

Currently, our primary problem with recurrent disease is focused on hepatitis C. Any patient that enters transplantation with hepatitis C virus circulating in their blood will have ongoing hepatitis C after transplantation. However, those who have completely cleared their virus and do not have measurable hepatitis C in the blood will not have hepatitis C after transplantation.

Unlike hepatitis B where recurrent disease leading to liver failure occurs very rapidly, recurrent hepatitis C typically causes a more gradual attrition of liver function. Only a small percentage of hepatitis C recipients, approximately 5%, return to cirrhosis and end stage liver disease within two years of transplantation.

Most have more gradually progressive disease such that as many as half will have cirrhosis at approximately 10 years after transplant. Interferon preparations in combination with ribavirin, widely used in pre-transplant hepatitis C patients, can also be prescribed after transplantation. Chances for permanent cure are somewhat lower than treatment before transplantation. Moreover, the treatment is associated with a significant complement of side effects. Recurrent disease is responsible for the fact that hepatitis C liver transplant recipients have worse medium and long-term post-transplant outcomes compared to liver transplant recipients without hepatitis C.

Several other diseases may also recur after transplantation, but typically the disease is mild and only slowly progressive. Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) both recur approximately 10-20% of the time and, only very rarely, result in recurrent cirrhosis and end stage liver disease. Perhaps the biggest unknown in today’s age is fatty liver disease after transplantation as it is clearly a problem of increasing frequency. Fatty liver disease can occur in those transplanted for NASH but also in patients who were transplanted for other indications and develop risk factors for fatty liver disease. The frequency, trajectory, and prognosis of recurrence of fatty liver disease after transplant and its course are active areas of research.

Opportunistic Infections and Cancer

As previously stated, the immune system’s primary role is to identify and attack anything that is foreign or non-self. The main targets were not intended to be transplanted organs, but rather bacteria, viruses, fungi, and other microorganisms that cause infection. Taking immunosuppression weakens a transplant recipient’s defenses against infection

As a result, transplant recipients are at increased risk to develop not only standard infections that may affect all people but also “opportunistic” infections, infections that only occur in people with compromised immune systems. The changes in the immune system predispose transplant recipients to different infections based on the time relative to their transplant operation.

They can be divided into three periods: month one, months one to six, and beyond six months. During the first month, infections with bacteria and fungi are most common. Viral infections such as cytomegalovirus and other unusual infections such as tuberculosis and pneumocystis carinii are seen within the first six months.

In addition to fighting infection, the immune system also fights cancer. It is believed that a healthy immune system detects and eliminates abnormal, cancerous cells before they multiply and grow into a tumor. It is well-recognized that transplant recipients are at increased risk for developing several specific types of cancers.

Post-Transplant Lymphoprolipherative Disorder (PTLD)

Post-Transplant Lymphoprolipherative Disorder (PTLD) is an unusual type of cancer that arises exclusively in transplant recipients, as suggested by its name. It is almost always associated with Epstein-Barr virus (EBV), the same virus that causes infectious mononucleosis or “the kissing disease.”

The majority of adults have been exposed to EBV, most commonly in their childhood or teenage years. For these patients, EBV-associated PTLD can develop after transplantation because immunosuppression allows the virus to reactivate. In contrast, many children come to liver transplantation without ever having been exposed to EBV. If patients are exposed to EBV after transplantation and therefore under the influence of immunosuppression, they may be unable to control the infection.

PTLD arises in either scenario when EBV-infected B cells (a subset of lymphocytes) grow and divide in an uncontrolled fashion. As it is fundamentally a result of a compromised immune system, the first line of treatment is simply stopping or substantially reducing immunosuppression. While this approach frequently works, it also risks graft rejection which would then necessitate increased immunosuppression. Recently, a drug that specifically eliminates B cells, the cells infected by EBV, has become available.

Today, a common approach is therefore to give this drug, rituximab, in conjunction with less drastic cuts of the immunosuppression drugs. If this approach does not control PTLD, then more conventional chemotherapy drug regimens typically given to treat lymphomas that develop in non-immunosuppressed patients, are used. The majority of PTLD cases can be successfully treated with preservation of the transplanted organ.

Non-Melanoma Skin Cancer (NMSC)

Skin cancers are the most common malignancy in the post-transplant population. The rate of skin cancer in patients who have undergone organ transplantation is 27% at 10 years, reflecting a 25-fold increase in risk relative to the normal population. In light of this substantial risk, it is strongly recommended that all transplant recipients minimize sun exposure.

Moreover, all transplant recipients should be regularly examined to ensure early diagnosis and expeditious treatment of any skin cancer. There is some evidence to suggest that sirolimus, an immunosuppressant in the class of mTOR inhibitors does not increase risk of skin cancers.

Therefore, transplant recipients who develop multiple skin cancers can be considered for a switch to a sirolimus-based, calcineurin-inhibitor free immunosuppression regimen. Currently, there is no data to indicate that liver transplant recipients are at increased risk to develop other common cancers such as breast, colon, prostate, or other cancers.

Risks and side effects of liver transplant

Like partial hepatectomy, a liver transplant is a major operation with serious risks and should only be done by skilled and experienced surgeons. Possible risks include:

• Bleeding
• Infection: People who get a liver transplant are given drugs to help suppress their immune systems to prevent their bodies from rejecting the new organ. These drugs have their own risks and side effects, especially the risk of getting serious infections. By suppressing the immune system, these drugs might also allow any liver cancer that had spread outside of the liver to grow even faster than before. Some of the drugs used to prevent rejection can also cause high blood pressure, high cholesterol, and diabetes; can weaken the bones and kidneys; and can even lead to a new cancer.
• Blood clots
• Complications from anesthesia
• Rejection of new liver: After a liver transplant, regular blood tests are done to check for signs of the body rejecting the new liver. Sometimes liver biopsies are also taken to see if rejection is happening and if changes are needed in the drugs that prevent rejection.