Peritoneal Surgery

While it is the primary tool for treating peritoneal mesothelioma, surgery, by itself, is not considered curative. The abdomen is a complex space, filled with a variety of easily damaged and extremely important organs. A cancer affecting the abdominal lining, or peritoneum (paira-tin-e-um) is therefore a very serious and hard to treat matter.

The peritoneum is made of two parts, the visceral and parietal peritoneum. The visceral peritoneum covers the internal organs and makes up most of the outer layer of the intestinal tract while the parietal peritoneum covers the abdominal cavity.

While both the pleural (chest) and the peritoneal (abdominal) space contain the same lining and suffer from the same cancer, the nature of the two spaces dictates that different treatment strategies must be used. The peritoneum is located in an area of soft tissues, easily accessed and pliable, where the pleura is found inside a rigid space (the rib cage) and is difficult to reach without cutting through bone. Thoracic (chest) surgery to remove the pleura almost always involves the permanent removal of at least one rib.

The peritoneal and pleural mesothelial cells are designed to provide lubricating secretions which allow the organs in each respective space to move freely. When the cells of the mesothelium malfunction due to the cancer's progress, an overproduction of this fluid often results. This is called ascites and causes many of the symptoms discussed earlier in the diagnostic section.

Unique structures inside the abdomen make treating peritoneal mesothelioma both more difficult and, in some ways, easier than pleural mesothelioma. There are two folds of the peritoneum called the greater and the lesser omentum.  These structures serve to connect the viscera and provide support for blood vessels.

In most mammals, the great omentum forms a great sac, which is attached to the transverse colon and the stomach. It is loaded with fat, and covers nearly all of the intestines. The lesser omentum connects the stomach and liver and contains the hepatic vessels. There is also a ligament called the gastrosplenic omentum which connects the spleen and stomach. If the omentum is heavily encrusted with mesothelioma it may be necessary to remove it, changing the structure of the abdominal space quite dramatically.

On a comparative basis, therefore, the abdomen has a much larger surface area than the chest to be treated. Using a geographic analogue the chest is like a smooth coastline and the abdomen is like a coast covered with inlets and islands. The latter offers far more miles of coastline than the former. This, together with the complexity of the space and fragility of the organs such as the bowels, leaves little chance for surgically resecting all of the tumor. 

The relative ease of access to the abdomen has numerous interesting benefits, however. The stomach wall can easily be entered to allow access to the abdominal space and this means that the area can support multiple debulking surgeries and inspections to keep the tumor in check. It also means that the area can be treated with innovative techniques such as heated chemoperfusion, gene therapy, immunotherapy and photodynamic therapy. 

Consequently, a very successful strategy for treating peritoneal mesothelioma has emerged that combines aggressive debulking of the tumor with one or more of the other techniques as adjuvants.

Several treatment centers now offer peritoneal treatment that involves several courses of surgery over a specific interval, with chemotherapy, radiation or other treatments either during or after the surgeries. Success with this approach has been excellent and there are now a number of long term 7+ year survivors of peritoneal mesothelioma as proof of the value of this multimodality approach.

The technique of using heated chemoperfusion to attack the residual mesothelioma tumor in the abdominal space was pioneered by the peritoneal surgeons and then was applied to the pleural mesothelioma environment where the strategy is also meeting with success and extended survival times. 

Chemotherapy Treatments

The principles behind treating cancer with chemotherapy are a bit like a scorched earth strategy, denying the enemy sustenance in the expectation that cancer needs resources more than healthy tissues do.

Most cancer chemotherapy is applied systemically, meaning it is applied to your whole body via the circulatory system. The easiest way to deliver systemic chemotherapy is to ingest it in pill or liquid form via the digestive system. This approach works only for those chemicals that can survive the rigors of being digested in the stomach, and then only if the molecules are small enough to be absorbed into the circulatory system by the intestines.

The molecular structures of many chemotherapy agents are too fragile to allow the drug to be taken this way, or they are too large to be absorbed into the blood stream through the intestines. Therefore, most chemotherapies are given by an injection or an intravenous drip along with saline solution on a specific timetable. Your entire body is therefore exposed to the effects of a systemic poison and not just the cancer in a specific location. This can be an important benefit of a systemic treatment if the cancer has already metastasized and begun to move to secondary areas or other organs. Once in the blood stream, the chemical agents can go wherever your circulatory system can reach.

Since organs like the brain, kidneys, lungs, and liver are also exposed to the toxic effects of these drugs, dosages need to be carefully controlled so as not to kill healthy cells along with the cancer cells. Antidotes can also be given in advance for some chemotherapy agents that are known to carry high risks of morbidity to organs like the kidneys or liver. Since excreting these systemic poisons as quickly as possible is important, having healthy kidneys may dictate whether chemotherapy is an option.

The most effective alternative to systemic application is a regional or localized application where higher doses of the drugs can be administered directly to the affected area or organ. There are two variations to this technique of controlling the application of chemotherapy to specific surfaces. The first method is direct application and the second is intra-cavitary application via a special shunt or tube that is used to feed the chemicals directly into the peritoneal space. Both of these techniques allow much higher doses of chemicals to be used since most of the drug remains outside of the bloodstream, coating only the exposed tissue surfaces.

Some absorption of the chemo into the affected surfaces is necessary for it to work. For chemotherapy given in this manner during surgery, the surgeon will sometimes take tissue samples to analyze how deeply the drug has penetrated the tissue wall. Since penetration of the cell wall implies some entry of chemo into the bloodstream, the use of an antidote is an important precaution.

Which approach is used depends upon the goals of the treatment and the need to control side effects. In any case, the application methods are carefully selected to ensure that more damage happens to the cancer cells than to the healthy cells. Chemotherapy works because the rapid growth of cancer cells makes them more vulnerable to chemicals that block, destroy or interfere with fast growing cells.

Chemotherapy Actions:

Chemotherapy agents can act in two principal ways: disrupting cell reproduction (cell division) or physically destroying cancer cells. The process of cell reproduction is complicated and has several different and distinct stages. The first treatment approach uses chemotherapies that act at several different times during cell replication process. Such drugs are called Alkylating agents.

No matter how its done, when a cancer cell is blocked from replicating itself, the tumor stops growing. Unfortunately, many of these agents will have that effect on ANY fast replicating cell. Since we cant protect our healthy fast replicating cells, sperm, white and red blood cells, we often get nasty side effects such as low blood counts that may interfere with treatment if unresolved.

Recently, research scientists have discovered ways to begin producing chemical agents that only target specific types of cells. In some cases it has been possible to target specific subgroups of cancer cells, known to replicate themselves by using a specific receptor. One day soon, we hope to have unique chemical poisons for each type of tumor. Then we can spare the regular cells from the side effects of the treatment. Such targeted chemotherapies are not yet in standard clinical use but are being investigated in clinical trials.

Chemotherapy Side-Effects:

Chemotherapy can be strong medicine and the strain it places on the body can demand that a patient have a strong stomach, heart, liver, and kidneys. All are essential to help the patient absorb, circulate and then eliminate these chemicals from the body and still recover from the damaging side effects of the treatment. For many patients, reduced white cell counts, red blood cell counts and reduced platelets can all be evidence of systemic damage caused by chemotherapy.

Most patients suffer some measure of immune suppression because chemotherapy affects the bone marrow, where white blood cells are produced. There are a number of drugs available which can help restore red blood cell production, boost the production of white blood cells or help platelet production.

Weak immune systems can be helped by taking flu shots, pneumonia vaccine and other such measures to boost the bodys ability to fight infection before the chemotherapy regimen begins. Even the secondary effects of chemotherapy, nausea, vomiting and loss of appetite, fatigue and changed taste and smell, can be aided with modern counter-medicines, which can ease these symptoms. Consult with your doctor about what options are available for you, should you be facing a series of chemotherapy treatments.

Why Don't Chemotherapies Cure Meso?

For reasons that arent entirely understood yet, chemotherapy works differently for nearly every patient. In some cases the difference can be dramatic. Certain drugs can make a major impact on one persons tumor but have absolutely no effect on the next. To date, the biggest obstacle to treating peritoneal mesothelioma with chemotherapy alone is either that the amount of tumor present is too large for the chemo to destroy it or that the tumor develops resistance to the chemo. Surgery can assist with the first problem by reducing the tumor remaining to a manageable amount that chemo can handle.

It is the second problem that is so intriguing and holds so much promise. It appears that not every tumor cell uses the same pathways to grow and to spread. Attacking some but not all of the pathways used by the tumor to replicate will reduce only a portion of the tumor burden, allowing the tumor that is left to grow unimpeded. This is the primary reason single chemotherapy protocols don't cure the tumor and seem to stop working after a number of months. Using multimodality chemotherapy treatments seems to be much more effective since it attacks multiple pathways at once, allowing the tumor no room to evade treatment. Once all the pathways have been identified and drugs found that will interfere with them, it may be possible to use chemo alone as a curative treatment. 

Our current knowledge of the development of cancer has established that each tumor is a reflection of the different genetic makeup of the host individuals cells.  Recently, attempts have been made to grow test tube cultures of a persons tumor and then expose them to a variety of chemical solutions in vitro (in a test tube solution). The problem appears to be that success in the test tube doesnt always translate into an effective tumor fighting treatment when it is tried in vivo or in a live subject. A vigorous debate is underway as to whether this approach has merit or not.

Chemotherapy protocols have changed and continue to change quickly. Multimodality treatment employing surgery, with Gemcitabine (Gemzar) Cisplatinum, Carboplatinum and other chemotherapies are now being adapted to use monoclonal antibodies like Iressa and Tarceva as well as anti-angiogenesis drugs like bevacizumab and endostatin as well as new targeted drugs like deacetylase inhibitor SAHA, to attack the tumor from multiple directions at once. Drugs like Interferon, Thalidomide and Cox2 inhibitors like Celebrex are being tried in various combinations to boost the effectiveness of chemotherapies.

The arrival of Alimta, the first drug that showed a significant response in mesothelioma as a single agent is now being tested in clinical trials looking at combination therapies.

Radiation Treatments:

Radiation has proved to be of limited use in abdominal mesothelioma as a primary treatment but has proved useful in preventing malignant seeding of the incision sites. Its use is highly recommended in both pleural and peritoneal mesothelioma to prevent the appearance of mesothelioma in the area of surgical incisions.

Because of the easy access to the peritoneal cavity, some consideration has been given to using photodynamic therapy as an adjuvant treatment for peritoneal mesothelioma. The surface to be treated is bathed in a chemical that is absorbed by both healthy cells and tumor cells. Healthy cells tend to clear this chemical more quickly. The chemical sensitizes cellular tissues to exposure to light, causing apoptosis or cell death. If timed correctly, only the cancer cells self destruct because only they retain the sensitizing chemical. Clinical trials for this have been attempted but the results aren't convincing enough to make this a standard therapy.