Pleural Surgical Techniques
While both the pleural and peritoneal 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 pleura is found inside a rigid space (the rib cage) and is difficult to reach without cutting through bone. Thoracic surgery to remove the lung and/or the pleura almost always involves the permanent removal of one rib and sometimes more.
There are two primary surgical protocols used in treating pleural mesothelioma:
In P/D the surgeon removes the lining of the parietal and visceral pleura, the lining of the chest and the lung. EPP involves en bloc resection of the paritietal and visceral pleura along with the involved lung, medstinal lymph nodes diaphragm and pericardium. Both procedures may remove part or all of the diaphragm and the pericardial sac (the exterior lining of the heart sac) and they are replaced by patches made from bovine tissue or Gore-Tex, an impermeable fabric used for tents and clothing. These procedures have a profound affect on the patient both physically and psychologically. Many patients opt to enlist the help of a psychologist to help them cope prior to and following the surgical procedure. It is difficult to predict what the recovery process will be like but many patients do make a full recovery following these procedures. This being said, one must keep in mind that this is not a curative procedure but one that can contribute to an extended survival.
Before these two procedures are performed, a series of tests must be performed to determine that they can withstand the rigors of the surgery. The contralateral lung is examined and must demonstrate the capacity to take over pulmonary function once the affected lung is removed. Likewise cardiac function is assessed as the strain on the heart during and following this procedure is not insignificant. Full body scanning is required to rule out disease that would lie outside of the operative field. In some cases the surgeon might do a laproscopic procedure in the peritoneum or chest should there be a questionable area found on scan. Once these tests are performed and the results deemed satisfacoty the patient may move on to surgery. The type of surgery planned is often not the surgery performed. In many cases the panned PD is changed to an EPP as disease may be found that is not amendable to a PD.
Despite the presurgical work up many patients are found to have unresectable disease and the operation is abandoned To undergo surgery of this magnitude, a patient needs to have a healthy heart, a viable second lung and, in the case of adjuvant chemotherapy during surgery, strong kidney functions and a healthy liver. Age, general health and the condition of the respiratory system, histology, extent of disease at the time of surgery all have a direct bearing on the outcome of the surgery and ensure that morbidity and mortality rates are kept as low as possible. There is great controversy as to which procedure should be offered to eligible patients and much discussion is taking place among the experts in this disease in trying to determine what prognostic variable make a particular patient more likely to benefit form surgery. Patients are therefore encouraged to seek an opinion from both a medical oncologist and a surgical oncologist who have developed an extpertise in mesothelioma. Full discussion of risks vs benefits need to be addressed at these consultations plus ample time for questions to be asked.
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Special care must be taken to protect the heart during these surgical procedures and during radiation therapy which is often part of the planned protocol.. . The heart is handled and stressed by the removal of the pericardium and this may result in an arrhythmia. In some cases, bleeding may occur into the heart sac, a condition called cardiac tamponade.
Equally serious but rarer problems are allowing air to find its way into the lung, having fluid leak from the chest cavity into the remaining lung, or fluid leaking into the bronchial tube. Infections or bleeding inside the chest cavity are always risks, as are contracting pneumonia in the remaining lung, or developing air leaks after stripping the lung of its pleura during a P/D procedure.
While both P/D and EPP should be considered major surgery, on a par with open heart or brain surgery, these protocols, when performed by experienced medical teams, and supported by expert and experienced nursing care, can be the best chance for an extended survival inpleural mesothelioma. Studies are currently ongoing to improve surgical results as well as studies to predict which group of patients will benefit from which type of therapy be it surgery, chemotherapy or a combination of both. The role of radiation and type of radiation to be applied in these procedure is also being investigated. We encourage patients to consider these treatment modalities only at specialized centers who have published the results of their surgical series in peer reviewed journals, and are currently conducting clinical trials in PD or EPP.
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Chemotherapy in mesothelioma is not curative. That is not to say that chemotherapy is not without benefit to the patient affected by mesothelioma. Studies have demonstrated that the most active regimen can reduce tumors in 40% of patient and extend life in those that respond to chemotherapy. Chemothery has also been shown to palliate symptoms including reducing shortness of breath, reduction of ascites or effusions, reduction of pain and improvement has been noted in quality of life studies. Chemotherapy is also given as a neo adjuvant treatment (prior to a planned surgical intervention) post surgery(adjuvant therapy) or as a single modality. In some cases patient who have been considered inoperable can become surgical candidates following administration of chemotherapy.
Some chemotherapy is cytotoxic which means that it is capable of killing malignant cells, others are cytostatic which means that it can inhibit cellular activity or cellular multiplication. We now use a new term “targeted” therapy or “smart” drugs which refers to drugs that are specifically designed to act on genes that promote or suppress canceous cells. Immunotherapy is a method of harnessing the bodies own immune system to activate and kill malignant cells. A thorough discussion will take place in a section titled ‘Standard and Investigational Therapies in Mesothelioma'.
The most effective alternative to systemic application is a regional or localized application where penetration of the drug can be administered directly to the affected area or organ can reach levels much higher than through the systemic circulation. 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 pleural space. Both of these techniques allow much higher concentration of chemicals to be achieved 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 need to strip the tumor down to millimeters to ensure optional tissue penetration. Doseages of some of the drugs used in this manner have been determined by tissue penetration studies in mesothelioma and other cancers.
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 and should be made available only in a clinical trial setting. Experienced mesothelioma centers are the best suited to advise on the benefits vs the risks of these procedures as well as the experience to minimize the risks adherent to the vairious protocols. EPP and PD are not standard of care but options to be considered during initial consultations.
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.
No matter how it's 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 can’t protect our healthy fast replicating cells, sperm, white and red blood cells, we often get side effects such as low blood counts that may interfere with treatment if unresolved. Prior to initiating treatment referrals to fertility specialists is suggested for those in their reproductive years. Not all chemotherapy renders a patient infertile and drug selection can be discussed in those who wish to preserve fertitlity. Consultation with a cancer geneticist is recommended to guide patients as they make these difficult decisions.. We are now observing extended survivals and younger patients are presenting with mesothelioma so preservation of fertility has become an area of concern.
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 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.
A misconception among cancer patients is that they only need to see their medical oncologist or surgeon. Patients will still require an internist to maintain their regularly scheduled yearly interventions. Flu and pneumonia vaccines continue to be recommended on the suggested schedule. Contiguous cancers have been reported which make screeing crucial for second malignancy in those commonly reported cancers breast, colon, prostate and lung ie,; physical exam, colonoscopy, mamagraphy and fecal occult stool testing. Patients are surviving longer with mesothelioma so keeping up with your general health is equally important.
There are new drugs in development and approved frequently to help in the management of chemotherapy related side effects. Chemotherapy attacks the fastest growing cells in the body so normal cells can also be affected. Frequent monitoring of the blood counts is performed and in some cases growth factors are initiated to stimulate the production of red blood cells and white blood cells. These can diminish the fatigue associated with anemia and lower the risk for infection while on systemic treatment. Targeted therapies can be associated with skin rashes, elevated blood pressure and fatigue. Medications will be prescribed to control for these systemic symptoms.
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 pleural 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. Development is underway testing a patient’s individual pathology to look for markers that are known to be resistant to certain chemotherapy drugs. This would enable the oncologist to select a drug based upon the genetic profile of the patient. This is one of the most promising fields of investigation.
Chemotherapy protocols have changed and continue to change quickly. Please refer to the section titled Chemotherapy Treatment for a discussion of current therapies and some under investigation.
Radiation has proved to be useful as an adjuvant to EPP with extended survivals reported in large tertiary centers. The types of radiation that should be used are currently under investigation. Some centers are testing IMRT (intensity-modulated radiation therapy), photodynamic therapy, and adjuvant hemothoracic radiotherapy. The best use of radiation therapy following an EPP has yet to be clearly defined. It is difficult to give radiation therapy following a PD as the damage to the lung can be extensive. Studies are underway to see if IMRT might be useful in this setting. Radiation therapy using any of these techniques has the risk of causing radiation pnemonitis to the remain lung post EPP or to either lung following a PD. Only an experienced radiaologist at a major center should be considered to apply this treatment option.
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