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Thursday, May 10, 2007


Diagnosis of mesothelioma is difficult because the disease often isn’t visible on external scans and the symptoms may be confused with a number of common ailments that misdirect the medical staff and defer more thorough investigations. Once mesothelioma is suspected, a definitive diagnosis requires a tissue biopsy, a complicated, somewhat risky and expensive process.

The process of diagnosis usually begins with some form of radiological investigation. In pleural cases, where respiratory distress is the primary symptom, doctors may fall back on an x-ray to check for pneumonia or shadows on the lung indicative of tuberculosis or lung cancer. It is during this stage that fluid in the pleural cavity is first detected and invasive investigations first begin.

Other external examinations offer greater resolution and accuracy than X-Rays. The primary vehicle for external radiological examination is the Computed Tomography scan or CT examination. Computed tomography involves a series of precisely calibrated X-rays to be taken and received by electronic means rather than photographic film. These images are then reconstructed by computer to offer a highly detailed view of the body in narrow slices, allowing a look inside the body at anatomical details not otherwise visible without surgical examination.

Figure H: PET/CT Fusion showing combined images. The red cross in the human image shows hot spot. The slices show (from left to right) CT scan, PET scan and Combined fusion scan. Click here for enlargement. Photo courtesy K. Brauch.

CT scans are excellent at showing topography but cannot distinguish between scar tissue or tumor. While they can detect pleural or peritoneal thickening, the results aren't usually definitive enough to allow for a mesothelioma diagnosis with CT scan alone.

Another tool of importance in external exams is the Positron Emission Tomography scanner, or PET. PET is a process where radioactive glucose is injected into the bloodstream, where it is consumed in the greatest proportion by the most active parts of the body. This usually means the brain, heart, sex organs and tumors, if present, will consume the largest amount of this isotope, causing hot spots to appear on a scanned image of the body.

Tumors tend to be extremely active and therefore consume large amounts of the sugar isotope. This will cause hot spots to appear where they normally shouldn't, allowing the radiologist to identify possible indications of cancer.

Although PET scans can show activity, they are rather indistinct and cannot clearly identify the exact location of the activity. Simply put, CT scans can tell where a growth is located and PET scans can tell if there is excessive biological activity. The latest technology combines both the CT scan and the PET scan into a single computer image. Therefore, taken together, the PET/CT fusion scan produces a much more accurate image of activities inside the body. If an area of thickening is actively consuming sugar it may be cancerous. If the activity level is low or normal, it may simply be inflammatory response to injury, healing or other benign activity.

Figure I: PET/CT slice showing tiny central hot spot and presence of EPP (removed lung) in left of image. For Enlargement click here. Photo courtesy K. Brauch

Magnetic Resonance Imaging (MRI) and Ultrasound are both soft tissue scanning tools that are generally little used in diagnosing mesothelioma. MRI is sometimes used to determine if mesothelioma has penetrated through the diaphragm into the abdomen. In most cases, the images are considered too indistinct to be of much clinical value. Ultrasound simply doesn't penetrate deeply enough to be a good clinical tool in this setting. Despite the progress, such external tests aren't yet definitive enough to allow diagnosis without biopsy. Even if a tumor is detected, it must be examined by a pathologist to determine what kind of tumor it is and whether it is mesothelioma or some other type of cancer.

One of the first physical examinations to be conducted is the examination of fluid from the chest or abdomen. Fluid extractions from the chest via needle (thoracentesis) are performed for two reasons, to relieve the buildup of fluid and to provide a sample for a cytological examination. Unfortunately, examinations of the pleural effusion or abdominal ascites are only rarely conclusive. The sample would have to contain discarded tumor cells, something that would take luck to find. A diagnosis of mesothelioma can only be made from pleural fluid in about 33% of cases, so a definitive diagnosis is difficult without invasive surgery and a tissue biopsy.

Needle biopsies are also poor indicators since the mesothelioma tumor can be quite diffuse and thin. Hitting a tumor nodule with the biopsy needle from outside of the chest requires luck as well as skill. The principle means of obtaining a pathology specimen is through surgery and in most cases this involves video assisted surgery. For pleural mesos the surgery itself is called a thoracotomy (chest incision) followed by a thoracoscopy (fiber optic exam of the chest). For abdominal biopsies the surgery is called a laparotomy and laparoscopy (fiber optic exam of the abdomen). These procedures are in themselves difficult surgeries that are only offered in the event a serious illness is suspected. Since the symptoms of mesothelioma are often confused with other, more benign, illnesses, many people either don’t receive them or receive them only after long delays, affecting the prognosis of their cancer.

In an attempt to improve diagnosis of lymph node involvement, some institutions will require a mediastinoscopy to biopsy the lymph nodes in the chest. This procedure is day surgery and a finding of positive lymph nodes might influence a decision not to offer surgery since the surgical staging would be at least stage 3.

Diagnostic examinations may or may not involve rudimentary treatment attempts. In pleural cases, many surgeons opt to perform a pleurodesis (scraping of the tumor) procedure and the injection of abrasive material, like talc, for example. The purpose of this is to irritate the site and stimulate the formation of scar tissue which will enclose the tumor and prevent further weeping of fluid into the body cavity. If the fluid accumulation isn’t stopped, it leads to secondary problems such as compression of the lung, compression of key blood vessels and arteries. Untreated, the fluid accumulation may lead to serious and life threatening complications long before the tumor itself is fatal.

After the thoracotomy, the surgeon will temporarily install a tube, placed in the opening and sewn air-tight to the skin, to allow the remaining fluid and blood from the surgery to drain. This tube may also be used longer term in patients who are receiving chemotherapy and require long term management of the effusion as an alternative to repeated thoracentesis procedures.

In late 2004, a serum test for mesothelioma was released by Fujirebio Diagnostics in Australia and Europe called Mesomark™. This blood test checks for elevated levels of a blood serum marker called Serum Mesothelin Related Protein (SMRP) and with further validation and refinement, this test may prove to be a viable alternative method for identifying the presence of mesothelioma. SMRP was the subject of a Meso Foundation grant to investigate its validity in a study of the residents of Libby Montana. (See Meso Foundation press release and press release about European distribution of the test.) Mesomark is not yet available in the United States or Canada.

In the spring of 2005, a research article in the New England Journal of Medicine touted the discovery of another possible mesothelioma serum marker called Osteopontin. Researcher Dr. Harvey Pass felt that the two markers might be complementary to each other and assist with the future diagnosis of mesothelioma. Serum tests will be valuable for allowing non-intrusive tracking of residual tumor or monitoring for recurrence in patients who have been treated for the disease.

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