Source: CD200: A Putative Therapeutic Target in Cancer

One of the most exciting developments in cancer research is the increasing knowledge we have of the biological and biochemical processes involved in tumor development. Scientists are still years away from fully mapping the structural components of tumors, but they have successfully identified a number of proteins that are overexpressed in a variety of malignancies. CD200 is one such protein. Previous studies have shown CD200 expression as a prognostic factor in acute myeloid leukemia (AML) and multiple myeloma (MM) and now, researchers from France writing in the journal Biochemical and Biophysical Research Communications have published their findings on CD200 expression in a number of other cancers. They conclude that CD200 is a viable therapeutic target for cancer treatment.

Introduction to the Study

CD200 is a transmembrane protein whose expression has been shown to have immunosuppressive effects on the body. Some of these previously identified effects include inhibition of macrophages, which are important immune-system cells that digest pathogens and other foreign bodies, as well as induction of regulatory T-cells that suppress immune system activation and the inhibition of tumor-specific T-cell immunity. CD200’s tolerigenic effect, i.e., its ability to restrict an immune system’s response to a foreign body, has also been demonstrated in mouse models. In those cases, CD200’s immunosuppressive effects were a benefit to therapy, as they led to an increased survival rate after tissue transplant. CD200 has been implicated in a number of other pathologies and malignancies as well.

To look at CD200 expression in other forms of cancer, the authors examined a number of public sources, including the Oncomine Cancer Microarray database (http://www.oncomine.org), the Amazonia database (http://amazonia.montp.inserm.fr/) and the Integrated Tumor Transcriptome Array and Clinical Data Analysis database (http://bioinfo-out.curie.fr/ittaca/).

The researchers analyzed the data in two ways:

1. Expression of CD200 in malignant tissues from a variety of cancers; and
2. In cases were expression correlated with the cancer, they looked at the relationship between expression and tumor progression/stage.

Conclusion

Regarding the overall correlation of CD200 and cancer, they found significant overexpression of CD200 in the following areas: renal carcinomas compared to normal kidneys; head and neck carcinomas compared to normal head and neck tissues; testicular cancer compared with normal testicular tissue; pleural mesothelioma compared to normal pleural tissue; and colon carcinoma compared with normal colon tissue. The authors also found a high correlation between CD200 and advanced-stage disease, especially with bladder cancer, advanced-stage lung cancer and chronic myelogenous leukemia. They postulate that CD200’s immunosuppressive effects are responsible for this latter development, as the cancer can develop or remain in the body without triggering an immune system response. More research is certainly needed on this topic, but the authors definitely conclude that CD200 is overexpressed in a number of cancers and is often associated with a bad prognosis.

Labels: cancer, mesothelioma

Source: Nakas A, et al., The role of video assisted thoracoscopic pleurectomy/decortication in the therapeutic
management of malignant pleural mesothelioma, Eur J Cardiothorac Surg (2007), doi:10.1016/j.ejcts.2007.09.039

Mesothelioma is among the most difficult cancers to treat effectively and no true cure exists for this asbestos-caused disease. However, there is an active and creative research community regularly exploring new therapies that hope to improve upon current mesothelioma treatments. Surgery is one of these active areas of research and doctors are regularly comparing mesothelioma surgical techniques in terms of their efficacy, survival time and recovery rate. Researchers from the United Kingdom have recently released the results of a study that looked at what the proper role of video-assisted thoracoscopic (VATS) pleurectomy/decortication should be in the treatment of malignant pleural mesothelioma.

Introduction to the Study

There are a number of surgeries in common use for the management of mesothelioma. They are generally split between two strategies: strictly palliative procedures, which only try to reduce the pain and increase the quality of life of a patient—but do not try to actually cure him or her, and life-extending procedures that aim to reduce tumor burden as much as possible to increase survival time and, ideally if not practically, to cure the patient of the disease. The two most common life-extending procedures used for the treatment of pleural mesothelioma are extrapleural pneumonectomy (EPP) and radical pleurectomy/decortication (Radical P/D). An EPP is defined as the en bloc resection (complete removal) of the affected lung, pleura, pericardium and diaphragm, with a corresponding reconstruction of the pericardium and diaphragm. A Radical P/D is similar to an EPP, but it leaves the lung intact. These procedures are associated with high morbidity, meaning they are prone to significant complications during and after surgery, and high mortality, which means there is a possibility that the patient may die during surgery or soon after it. They are still, however, the standard of care for certain patients because they offer the best chances to prolong survival.

The authors of the study compared these two procedures with video-assisted thoracoscopic pleurectomy/decortication (VATS P/D) to determine the overall efficacy of the procedure and to study what, if any, quality-of-life improvements arose for those who underwent it. The authors define a VATS pleurectomy/decortication as a pleurectomy of the parietal pleura and a decortication of the lung with removal of the visceral pleura. Unlike Radical P/D, the extrapleural areas are left intact. It is a debulking procedure designed to reduce tumor burden, but is considered more of a palliative procedure because it does not seek to remove all macroscopically-visible malignant tissue. It is a less radical procedure than either EPP or Radical P/D and is often given to older patients and/or to those who are unfit for the others.

The authors looked at the results of 208 patients who underwent surgery for pleural mesothelioma. 112 underwent an EPP, 29 had a Radical P/D and 67 had VATS P/D. 63 were over the age of 65 at the time of the operation and 42 of them underwent a VATS P/D. In terms of overall fitness, VATS P/D was given to those who did not quality for an EPP or Radical P/D.

Conclusion

In aggregating the study numbers, the authors discovered that for the over 65 group, 30-day mortality was much higher for EPP (23%-3 out of 13) than it was for Radical PD (12.5%-1 out of 8) and VATS P/D (7.1%-3 out of 42) . These mortality figures confirmed that, in at least some cases, VATS P/D showed a positive offset in the patients favor for a reduction in treatment morbidity due to less extensive tumor resection. The VATS P/D group had a significantly lessened post-operative hospital stay period as compared to the EPP group (14.3 days/avg. vs. 36.6 days/avg.), although it was slightly higher than the Radical P/D Group (14.3 day/avg. vs. 14 days/avg). The authors also found that mean survival for the over 65 group favored VATS P/D (14 months) over Radical P/D (12.4 months) and EPP (11.5 months).

The authors conclude that they will still offer EPP and Radical P/D to patients who are over 65, but that for those over 70 they are reluctant to offer EPP. For people who are not candidates for the other radical surgeries, they feel that VATS P/D is the only effective method available to palliate their situation. While VATS P/D has known quality-of-life benefits and appears to prolong survival in at least one subgroup of patients, they are not yet ready to conclude that it’s a truly effective treatment strategy and call for more research into the question.

Labels: mesothelioma

Source: New York Times

The New York Times is running an article on one of the most cutting-edge—and most expensive—cancer treatments: proton beam therapy. Hospitals are using particle accelerators, which are machines that accelerate subatomic particles to speeds nearly that of the speed of light, to shoot protons directly into tumors. Proponents of this therapy, such as Dr. Jerry D. Slater, the head of radiation medicine at Loma Linda University Medical Center in Southern California, feel it’s much more accurate than traditional radiation therapy using X-rays. Dr. Slater says that “every X-ray beam I use puts most of the dose where I don’t want it,” while proton therapy more directly targets the actual tumor. In 1990, Dr. Slater’s hospital, Loma Linda University Medical Center, was the first hospital to install a particle accelerator and has since treated over 13,000 patients. There are currently five other hospitals around the country using proton beam therapy and more than a dozen others have announced plans to build their own particular accelerators.

The technology, however, is not without controversy.

Installing a particle accelerator is an exceptionally expensive proposition. A large accelerator can weigh over 200 tons, demand 18 feet of reinforced walls to house it and cost over $100 million. While most doctors accept the theoretical model the techniques are based on, many doctors are still concerned with the great costs associated with its use. Studies have yet to definitely establish that it is any more effective than other treatments and the concern is that patients who could be treated equally well with traditional—and less expensive—technology will be directed towards proton beam therapy simply because hospitals needs to recoup the costs of their investment. For example, many centers are using proton beam therapy to treat localized prostate cancer where Medicaid will $50,000 for the therapy, which is double what would be paid for traditional x-ray therapy with similar efficacy.

The great hope for the technology revolves around its ability to more effectively target a tumor, as well as induce less significant side effects due to its greater accuracy. Until more and better data becomes available, the controversy will likely continue unabated, just as construction of more facilities will continue as well. If, however, the therapy does prove to be more effective and exhibit less side effects, patients and their families will have one more modality in their fight against cancer.

Labels: cancer

Source: The Buffalo News

A number of employees of the town of Amherst, New York were recently exposed to asbestos during demolition work performed as part of an upgrade of the town’s Sewage Treatment Plant. The employees were replacing failing filters at the treatment plant, which requires the removal of a concrete pipe that is attached to each filter. One of the employees became concerned that the pipe might contain asbestos, so they checked with the plant managers who verified that the pipe was made of concrete mixed with asbestos. The angry workers then complained to the town because they were not given the proper protective gear for working with asbestos. The town’s engineer, Jeffrey Burroughs, said that neither the town nor the plant’s mangers had any idea that the exposed pipes contained asbestos and had they known, they would never have knowingly exposed the workers without informing them. He said most pipes that used asbestos were buried underground and they were as surprised as the workers to see a pipe in the open.

The town has since sealed off the area and secured the necessary funds to bring in an asbestos removal contractor.

Labels: asbestos

Source: Australasian Radiology

One of the most difficult aspects of treating cancer is the distinct number of forms it can take. While most cancers follow particular biological patterns, the literature is full of examples that do not follow these general trends. For example, in patients who present with a number of different tumors, metastasis is most often suspected as it is very rare for a single person to have multiple primary tumors at one time. Another relative rarity is for one form of cancer to mimic an entirely different form. Imaging tests and morphology analysis can usually identify the type of cancer present in any one patient, but in some cases, these techniques may not return the proper diagnosis, so immunohistochemical (IHC) analysis may be necessary to properly identify the cancer at hand.

In a recent case study from Japan, doctors describe a man whose presentation violated both of the principles just described. The patient was diagnosed with pseudomesotheliomatous adenocarcinoma of the lung, which is a rare lung cancer that morphologically mimics pleural mesothelioma, as well as squamous cell carcinoma of the esophagus and adenocarcinoma of the stomach.

Case Study

The patient presented as a 78 year-old man with shortness of breath and right chest pain. He was a smoker without known asbestos exposure and while his previous medical history was generally insignificant, his presentation was quite remarkable. A CT scan revealed diffuse pleural thickening in the right thorax and PET showed significant pleural involvement. A biopsy of the pleural mass was performed by video-assisted thoracoscopic surgery (VATS). Pictures from VATS also showed pleural thickening with diffuse spread. All signs pointed to malignant mesothelioma. However, IHC analysis of the biopsy sample revealed adenocarcinoma of the lung, not mesothelioma. The final diagnosis given was pseudomesotheliomatous adenocarcinoma of the lung. This rare form of lung cancer has a similar growth pattern to diffuse malignant mesothelioma and typically shares its poor prognosis as well, with a median survival figure of eight months from diagnosis.

Along with the tests that revealed the pseudomesotheliomatous adenocarcinoma, the patient also underwent an upper gastrointestinal endoscopy, which is a procedure that allows a doctor to view and biopsy the interior lining of the esophagus, the stomach, and the duodenum (the first part of the small intestine). The procedure revealed tumors in the esophagus and the antrum, which is the cavity in the stomach where food collects prior to its passage into the small intestine. Biopsy of each tumor revealed they were separate, primary sites: the esophageal tumor was a squamous cell carcinoma, while the stomach tumor was an adenocarcinoma. Analysis of the stomach tumor and the pleural malignancy showed they, too, were separate primary sites, so metastasis was not involved in any manner with the patient’s presentation.

As there are no treatment guidelines for this combination of cancers, the doctors treated the man in a palliative manner. He died six months after diagnosis, due primarily to heavy tumor growth in the pleural areas.

Conclusion

This patient’s presentation was remarkable for having multiple primary cancers, as well as for one of them being pseudomesotheliomatous adenocarcinoma. When multiple tumors are present, metastasis is nearly always at work. The authors report on a previous study of 5456 autopsy cases that described 285 cases of double primary cancer (5.2%) and only 58 cases of triple primary cancer (1.1%). Immunohistochemical analysis clearly showed three primary cancers in this man, placing him within the 1.1% figure from the previous study. It should be no real surprise then that the authors also state this is the first case in the literature of pseudomesotheliomatous adenocarcinoma concurrent with esophageal cancer and stomach cancer. Pseudomesotheliomatous adenocarcinoma is itself a rare cancer. Morphologically it resembles pleural mesothelioma and its diffuse nature is unlike the majority of other forms of lung cancer, so it’s easy to mistake the one for the other. Immunohistochemical analysis is an effective means of differentiating the two cancers, as each presents with specific markers that IHC can identify. The authors recommend IHC in the diagnosis of any pleural malignancy because of its ability to accurately diagnose the particular cancer involved.

Labels: LungCancer, mesothelioma

Source: New York Times

The New York Times has published an article on one of the most contentious issues in current cancer research: are there specific stem cells that cause cancer, and if so, can treatments be developed that target these stem cells?

The basic hypothesis says there are certain types of cells that are responsible for the growth of tumors. These stem cells, which are different from and should not be confused with embryonic stem cells, renew their own malignant behavior, while also creating the conditions necessary for the development of a tumor’s actual mass. Only a small number of them would be necessary to start a cancerous event—or to sustain a growth—and they would answer the question raised by treatments that destroy most of a tumor but which don’t actually kill all of the cancer: if 99% of the tumor is destroyed, why does the cancer keep coming back? The idea, then, would be to develop treatments that target the stem cells instead of the whole tumor, as killing the stem cells would necessarily kill the tumor as well. Chemotherapy and radiation are actually quite good at shrinking and killing tumors, but they can’t always stop the cancer. If the stem cell hypothesis is true and effective treatments could be developed because of it, many doctors agree that it would constitute a revolution in cancer care.

However, the issue is as contentious as it is because not all doctors agree with the cancerous stem cell hypothesis. Those who don’t agree with it describe the belief that others have of it as bordering on the religious. They feel the science just isn’t in yet and are skeptical of the claims being made that research into cancerous stem cells will be a panacea for all forms of cancer research.

Thus, it is too early to tell if the stem cell hypothesis will be an actual revolution or just another well-intentioned idea that is swept into history, but results should start coming in soon. The National Cancer Institute has setup a $5.4 million research fund to look into cancerous stem cells and three major cancer centers—The University of Michigan Comprehensive Cancer Center in Ann Arbor, Baylor College of Medicine in Houston and the Dana-Farber Cancer Institute in Boston—are embarking on a preliminary study to test the hypothesis. Once the initial results from this study are in, doctors and scientists will have an opportunity to asses its results and critique its methods and, hopefully, the question will be on a firmer ground for analysis. All involved agree that as far as we’ve come in cancer research, there is still much that can be done to ease the burdens of and improve the treatments for those with cancer.

Labels: cancer

Source: Cancer Biomarkers

Soluble mesothelin-related peptides (SMRP) is a protein that has been identified as a potential tumor marker for malignant mesothelioma. A tumor marker is a substance produced by cancerous tissues that can be used to diagnose the existence of a malignant event, as well as to indicate the current state of the cancer. The ideal tumor marker will have at least two very important features:

1. It will only be produced by a single type of tumor, which will allow the diagnosis of particular cancers with perfect accuracy; and
2. It will be expressed from the beginning of the tumor’s life, which will make false negatives virtually impossible.

Few, if any, presently identified markers meet both of these requirements, but this research is ongoing and tumor markers represent some of the most exciting and promising work in cancer studies.

A number of previous studies have shown SMRP to have excellent potential as a marker for mesothelioma. Researches from Germany have recently released results of a study regarding the stability of SMRP under different lab conditions. Their goal was to understand the conditions under which SMRP would still be effective as a marker and under what conditions its efficacy would be compromised.

Introduction to the Study

To study the stability of SMRP and understand the parameters of its efficacy, the authors identified three variations that would impact a marker’s diagnostic value:

1. Biological factors, such as inherent intra- and inter-individual fluctuations.
2. Pre-analytical factors, such as handling and/or conditions of storage.
3. Analytical factors, such as assay imprecision.

To see how these factors would impact SMRP, they collected serum from 98 people, all of whom were considered healthy and none of whom had any known asbestos exposure. There were 47 men and 51 women. The serum was then stored under different conditions: 5 days at -80 degrees centigrade; 5 days at room temperature and then a number of thaw/freeze cycles over another 5 days. SMRP concentrations were determined using the MESOMARK ELISA kit. They used a number of statistical techniques to establish a baseline SMRP concentration in healthy people, which has been missing from previous SMRP research.

Results and Conclusions

The authors determined a baseline SMRP concentration between 1.5 and 1.6 nmol/L in the 95th percentile of the population. They noted that SMRP showed little variation to age-based biological variation, as overall concentration was statistically similar between those under 60 and those over 60. As regards structural stability due to storage conditions, the only significant differences involved those samples that experienced a high number (10+) of freeze and thaw cycles. They did not describe statistically significant findings when comparing serum stored at room temperature to serum stored at -80 degrees centigrade.

The authors confirm SMRP’s excellent potential as a tumor marker for malignant mesothelioma. They state that more work needs to be done, but that their results, combined with those of previous studies, show its potential to materially improve medicine’s ability to diagnose, and therefore treat, malignant mesothelioma.

Labels: mesothelioma

Belluck & Fox is pleased to announce that Judge James W. McCarthy of the Oswego County Supreme Court has ruled in favor of our client Paul Tuttle. Along with a number of other companies who sold asbestos-containing products, Belluck & Fox sued Gardner Denver on behalf of Mr. Tuttle for allegedly exposing him to pumps containing asbestos during his service with the United Status Navy. Gardner Denver moved for dismissal against Mr. Tuttle’s case on a number of issues, but Judge McCarthy denied their request, ruling that Belluck & Fox had presented strong evidence that warranted a trial (Paul Tuttle, et al. v. A.W. Chesterton Co., et al., No. 2006-5602, N.Y. Sup., Oswego Co.).

Judge McCarthy handles all of the asbestos cases in Syracuse, Oswego, Watertown, Utica and Rome.

Mr. Tuttle is represented by Joseph W. Belluck of Belluck & Fox.

Mr. Belluck said, “Companies like Gardner Denver should do the right thing and pay the veterans it exposed to asbestos—its right for our clients and for Gardner Denver’s shareholders.”

Labels: Firm, Press Releases

Source: Wall Street Journal

The Wall Street Journal’s health section is running an article on cancer patients and their families who are developing personalized drug combinations as a means of fighting their cancers. The article profiles the struggles of Neil Hutchinson, a forty-five year-old defense contractor, to save the life of his seven year-old son Sam, who suffers from neuroblastoma—a form of cancer that affects the sympathetic nervous system. Neil has taken an especially active part in Sam’s treatment and actually selected the individual drugs that make up Sam’s 44-pills-a-day drug cocktail. After reading stacks of books on neuroblastoma and hundreds of journal articles on its etiology and treatment responses, he developed Sam’s treatment regimen in consultation with his son’s oncologists and other doctors. While many medical professionals are uncomfortable with patients taking such an active roll in developing treatments, the Internet has allowed people to share anecdotes and other stories about effective treatments and, grudgingly anyway, the doctors will often acknowledge that it is precisely the personalized nature of the treatments that have allowed them to be effective for people.

Neil’s research into Sam’s condition has been the major factor in Sam’s cancer going into remission.

The idea behind drug cocktails for cancer is that instead of trying to develop a single agent that can stop cancer, its best to take a multi-focal approach and use a number of precisely-targeted agents to stop all of the various avenues in which cancer can grow. This treatment strategy should increase effectiveness and decrease side effects and it remains one of the most promising aspects of current cancer research. What has medical professionals most concerned about patients such as Neil and Sam are the devastating consequences that can happen when non-professionals spearhead a treatment regimen. They worry that in patients’ sincere attempt to get better they will actually be hurting themselves. Doctors also worry that if more people start their own treatments then enrollment in clinical trials will be reduced—which could have devastating consequences for the growth of medicine. If doctors and scientists can’t study enough people in a controlled setting, they fear the amazing treatment successes of recent years may not be replicated in the future.

Along with the Hutchinsons, the article discusses a number of other people who have also developed their own treatment regimens. While all acknowledge the controversy surrounding these developments, nearly everyone also agrees that in the battle against cancer, the most important thing to do is to fight the disease as creatively as possible.

Labels: cancer

Source: Minnesota Department of Health

58 taconite miners who worked in Minnesota’s Iron Range from the 1930s through the 1980s have been diagnosed with mesothelioma—a figure much higher than would be expected—as taconite is not considered as carcinogenic a mineral as asbestos is and whose relationship to mesothelioma is even more nebulous. In response to these diagnoses, the State’s Department of Health is embarking on a series of health studies in partnership with the University of Minnesota to study the conditions that have contributed to these illnesses.

The state has released a preliminary report regarding incidence rates and exposure factors that establishes the baseline figures that the future reports will draw from. In its press release regarding the report, the Department of Health states:

• Almost one-fourth of the 58 workers were employed in the industry for less than one year, while over a fourth were employed for 30 years or more.
• All but one of the miners who developed mesothelioma were diagnosed 30 years or more after they first went to work in the industry. In five of the cases, the time lag was 60 years or longer.
• The miners worked at locations scattered across the Iron Range, including all but one of the seven mining operations that were active during the period when they were employed. The exception—Inland Steel—employed only 618 of the 72,000 miners in the group being followed by MDH.
• Only three of the 58 miners ever worked at the former Conwed plant in Cloquet, which manufactured asbestos ceiling tiles between 1958 and 1974. The Conwed facility is believed to have contributed significantly to elevated mesothelioma rates in northeastern Minnesota, accounting for 25 cases of the illness among the 5,200 people who worked there.

Miners and their families are hoping the present and future studies will definitively establish the causes of the disease in these miners and that steps will be taken to better protect them.

Labels: mesothelioma

Source: Interactive CardioVascular and Thoracic Surgery

There are two primary surgical methods used in the treatment of mesothelioma: pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP). In a pleurectomy/decortication, the parietal pleura, visceral pleura, mediastinal pleura, pericardium and diaphragm are removed, leaving the lung as as intact as possible. An EPP involves a complete resection of the affected lung, along with the removal of the pleura, pericardium and diaphragm. As such, it is considered the more invasive of the two surgeries. In general, P/D has been used for patients in the earlier stages of the disease and EPP has been used in the later stages of the disease. However, surgeon bias has also had an important effect on the decision regarding which surgery to use and specific guidelines on when to use each procedure do not really exist. In an attempt to provide some guidance on this question, researchers in Japan have recently released the results of a study comparing the effectiveness of pleurectomy/decortication to extrapleural pneumonectomy.

Introduction to the Study

Mesothelioma remains a very difficult disease to treat properly. The disease is often undiagnosed until a fairly late stage and to date all available treatment modalities have had limited long-term success. However, there is active research in all areas of treatment, both in the development new treatments and in perfecting current treatments. As regards surgery, no guidelines have been definitely established as to when to use P/D or EPP or which has the better prognosis after the operation.

To analyze this question, the researchers looked at 87 patients with immunohistochemically-confirmed and histopathologically-confirmed malignant pleural mesothelioma. 65 patients were studied: 34 received a P/D, while 31 received an EPP. Of these patients, 58 were men and 7 were women. Histology showed 48 epithelial cases, 11 mixed cases and 6 sarcomatous ones. The latter two were grouped as a single variable so the comparison made was epithelial mesothelioma vs. non-epithelial mesothelioma. In terms of staging, 8 patients were Stage I, 13 were Stage II, 40 were Stage III and 4 were Stage IV.

Results

The authors did not find a significant difference in overall survival figures between P/D and EPP. For the 34 patients who underwent P/D, median survival was 17 months and three-year survival was 24%. For patients who underwent EPP, median survival was 13 months and three-year survival was 33%. Thus, patients who received a P/D had a longer median survival figure (17 months to 13 months), but a lower three year figure (24% to 33%).

When further comparing P/D to EPP, it was found that P/D was more often given to patients in the early stages (Stage I: 8, Stage II: 8) of the disease who presented with epithelial histology (29) than was EPP, which was not given to any stage I patients and only 5 stage II patients, and was given to 19 patients who presented with epithelial histology.

The study also included discussions not directly related to the P/D and EPP dichotomy. It once again confirmed that patients who present with an epithelial histological sub-type had a much better prognosis than those who present with mixed or sarcomatous histology. Median survival for the former was 18 months and three-year survival was 33%, which were clear improvements on the non-epithelial group where median survival was 8 months and three-year survival was 8%.

The study did not find a statistically significant difference in overall survivability between stage I and stage II patients, although it did note a marginal difference between stage II and stage III patients and a significant difference between stage III and stage IV patients.

When comparing all of the possible patients factors, the authors founds that older age, non-epithelial histology and late stage (III-IV) disease had a significant negative impact on survival.

The authors also noted that multimodal therapy with EPP provided excellent prognosis for the limited number of patients who underwent these procedures. Four patients underwent EPP with adjuvant hemi-thorax radiotherapy and five underwent an EPP with neo-adjuvant chemotherapy and adjuvant hemi-thorax radiotherapy. Eight of the nine patients survived and currently don’t show any signs of recurrence.

Conclusion

The study was designed to compare the effectiveness of P/D to EPP and to make recommendations on which procedure to perform. While it did not show any significant difference in survivability between the two procedures, the authors did note that P/D was more commonly used on those with early stage disease and epithelial histology, which has a better overall prognosis than does late stage and/or non-epithelial histology. The authors recommend that, given a patient who can tolerate both procedures, surgeons should attempt an EPP when possible, as complete resection of malignant tissue has the highest potential of achieving a complete cure. They also recommend, when possible, the use of trimodal therapy.

Labels: mesothelioma

Source: Regulatory Toxicology and Pharmacology

Asbestos is a term that covers a number of different mineral fibers. While they all share many similar properties and attributes, each fiber is individually distinct from the others in very particular ways, including shape, width and length. It has been known for decades that asbestos is carcinogenic and is the only confirmed cause of mesothelioma, but what has not been conclusively established are the carcinogenic properties of the individual fibers. Researchers in Canada and Australia have recently completed a study that attempts to answer some of these questions.

Asbestos Fiber Types

Asbestos fibers can be categorized into one of two main classes: amphibole fibers, which are characterized by long, needle-like fibers, and serpentine fibers, which are curl-shaped. Amphibole asbestos fibers include amosite, crocidolite, tremolite, anthophyllite and actinolite, while chrysotile is the only serpentine asbestos fiber. Even though the fibers are themselves structurally distinct, they are often found in the same mines so the different individual fibers can be mixed together in the mining process. For example, in many cases mining for chrysotile also resulted in tremolite findings, so studies on the health effects of chrysotile would have to include data on pure chrysotile as well as chrysotile contaminated with tremolite.

Asbestos Carcinogenicity by Fiber Type

Amphibole fibers are the most carcinogenic of asbestos fibers, seemingly due to their long, thin structure. Of these fibers, crocidolite carries the greatest risk for developing mesothelioma, as epidemiological surveys of crocidolite mines in South Africa and Australia have shown very high rates of mesothelioma and other cancers in mine workers in those areas. However, amosite and anthophyllite also show a risk of mesothelioma development in people exposed to those fibers. Tremolite, when mined for its own properties, as well as when found as a contamination element, such as the vermiculite mine in Libby, Montana which produced the greatest site-specific public health disaster in U.S. history, has a carcinogenicity similar to crocidolite.

Chrysotile is a serpentine fiber and for reasons still not fully understood, seems to present a reduced individual risk when compared to the other asbestos fibers. However, chrysotile was the most popular asbestos fiber used in the U.S., so its smaller overall carcinogenicity must be weighed against the much larger exposure concentrations that would be associated with its use here. The researchers note that authors of a previous study on asbestos carcinogenicity (Hodgson and Darnton) report a relative causation ratio for mesothelioma for crocidolite, amosite, chrysotile as 500:100:1.

Mesothelioma Risk Factors

As discussed above, the type of asbestos fiber a person is exposed to will have a great influence on his or her likelihood of developing mesothelioma in the future. The amphibole fibers are the most carcinogenic. As compared to them, chrysotile has a markedly lower risk, although it does still pose a risk. However, other factors also play an important role in the development of mesothelioma. Those factors include the duration and total amount of exposure, the time since first exposure and age at which it occurred, as well as the rate of elimination of fibers from the lung.

Of these risk factors, the number of years of regular exposure is a major component to the development of mesothelioma. The researchers state, “It is now reasonably well-established that the risk of mesothelioma increases with time since first exposure to the power of 3–4.”

Conclusion

Asbestos is a known human carcinogen that has claimed countless lives. While certain forms of asbestos carry greater risk for mesothelioma than do other forms, there is no such thing as safe asbestos. Being aware of the known risk factors for mesothelioma can help international workers and their families protect themselves if they are required to work around it.

Labels: asbestos, mesothelioma

Source: Biotechnology and Bioengineering

Asbestos detection is a process fraught with difficulty and many of the major modalities of identification have known limitations in their use. For example, phase contrast microscopic analysis, while it can detect some asbestos fibers quickly and easily, is difficult to use on the smallest particles and can have problems distinguishing asbestos from non-asbestos fibers. Other tests, such as electron microscopic analysis, are very effective for determining fiber type and analyzing even the smallest particles, but may require special skills for proper analysis, which limits one’s ability to quickly determine if asbestos is present in any given scene. In response to these limitations, as well as others not discussed here, researchers from Japan are developing an asbestos-detection technique that can be used quickly and accurately to detect asbestos fibers in clinical and on-site settings.

Introduction to the Study

There are several different types of asbestos fibers, so proper identification of fiber type is an important component in determining site-specific contamination figures and the overall health risks associated with the individual fibers. As stated above, there are a number of different techniques used, but each one has no problems in use. Because of this, a number of researchers are looking for more efficient identification mechanisms. The authors of this study had previously shown that E.coli ribosomal protein L2 binds to silicon or silicate particles, so they began to look for E.coli proteins that may bind with asbestos, itself a silicate mineral.

Results and Conclusions

The researchers found that the protein DksA was such a material. In developing a simple assay that can used on-site or in clinical settings, the researchers showed DksA’s ability to bind to chrysotile asbestos and to differentiate it from amosite, crocidolite or glass wool. The assay can identify asbestos contamination of a material in very small concentrations. The assay does not yet have the ability to bind to other asbestos fibers, but it can bind to chrysotile and therefore distinguish it from other, similar materials. The researchers state their assay is as effective as traditional x-ray analysis in detecting the presence of asbestos. Should their work succeed, asbestos detection may become cheaper and easier to accomplish.

The researchers hope to develop assays that can bind with and identify other forms of asbestos as well, such as amosite or crodidolite.

Labels: asbestos

Source: Scandinavian Journal of Work, Environment & Health

There is a considerable amount of anecdotal data stating that mesothelioma affects men and women in different ways. While men are much more likely to be diagnosed with this difficult disease, when women are diagnosed there seems to be some differences in origin site, prognosis and overall survivability as compared to men. Researchers in Australia have recently released results from a study looking at incidence trends between male and female patients with mesothelioma in New South Wales, Australia.

Introduction to the Study

To examine the incidence trends among male and female patients diagnosed with mesothelioma in New South Wales, Australia, researchers examined case files from the New South Wales Central Cancer Registry (NSW CCR) and the New South Wales Workers Compensation (Dust Diseases’) Board. The NSW CCR maintains a list of all cancer cases diagnosed in New South Wales since 1972 and notification of new cases is a statutory requirement. The Dust Diseases’ Board is a statutory authority that provides compensation for workers diagnosed with dust-related diseases who were employed in New South Wales. The Dust Diseases’ Board has compensated about 60% of the mesothelioma cases reported to the NSW CCR, so it reports a smaller series of numbers than does the NSW CCR.

Results

A total of 3090 mesothelioma cases were reported to the NSW CCR between 1972 and 2004. 456 of those were women’s cases, 2634 were from men. This leaves an incidence rate of 14% women, 86% men. Pleural mesothelioma, as would be expected, was the most diagnosed type of the disease. Of women diagnosed with mesothelioma, 15% had peritoneal mesothelioma, while only 6% of men were given that diagnosis. The Dust Diseases’ board has compensated 1995 mesothelioma patients over their history, with 95% of those compensated being men and women the remaining 5%. In terms of pleural vs. peritoneal disease, 94% of those compensated had pleural mesothelioma, while 5% had peritoneal mesothelioma.

Occupational data was never recorded for the NSW CCR, but it was recorded by the Dust Diseases’ Board. For men, the top five occupations most often represented in the mesothelioma compensation statistics were:

• Carpenter
• Fitter
• Trades assistant
• Electrician
• Asbestos Worker

For women, the top five occupations listed were:

• Steam press operator
• Process worker
• Clerical worker
• Textile machine operator
• Cleaner

The researchers did not find any gender-based difference in disease latency (M=43.7 years vs. W=42.8 years), but they did find a large difference between pleural and peritoneal mesothelioma, with peritoneal mesothelioma having a much shorter latency period. In men, latency between the two diseases was 38.8 years vs. 44 years and in women 29.7 years vs. 43.6 years. As would be expected, histological classification showed epithelial mesothelioma as the most common subtype and sarcomatous mesothelioma having the worst prognosis. Regarding long-term survival, statistics were poor, as is the case in the majority of mesothelioma diagnoses. Overall, women survived longer than men (10.4 months vs. 8.5). When broken down by gender and split between pleural and peritoneal disease, men did not see a statistically significant difference in survival between the two (pleural, 8.6 months vs. peritoneal, 5.6 months), but women showed a very significant difference between them (pleural, 9.3 months vs. peritoneal, 43.6 months). However, there were only 6 cases of women being diagnosed with peritoneal mesothelioma so the number may be too small to draw any conclusions from.

Conclusion

The results of the study have quantified much of the anecdotal data that exists on the differences between how men and women experience mesothelioma. The researchers once again showed the great difference in disease incidence between men and women, with men much more likely to be diagnosed. They found that women seemed to have a greater propensity for peritoneal disease than do men. They also found that women were more likely to present with epitheloid mesothelioma than either of the other two subtypes and they had a better survivability average, even if only slight. However, the clinical differences, especially in terms related to treatment and overall prognosis remain quite similar.

Mesothelioma remains a very difficult to disease to treat. Researchers around the world are hopeful that new studies and better research will increase both our knowledge of the disease and our ability to treat it.

Labels: mesothelioma

Source: Legal Medicine

A pleural effusion is a build-up of serous fluid in the spaces between the lungs and the chest wall and is the most common symptom of pleural mesothelioma. It can, however, be caused by a variety of other conditions, both benign and malignant, so an accurate diagnosis is essential for determining proper treatment. In many cases, a diagnosis is rendered based on cytological analysis of fluid smears and not by fine needle aspiration or surgical biopsy.

Introduction to the Study

Researchers in Italy conducted a study looking at the overall accuracy of cytological analysis to determine (a) whether the effusion was a benign or a malignant condition, and (b) if the effusion was malignant, could cytology then differentially indicate mesothelioma from another disorder, such as lung andenocarcinoma?

To complete this study, the researchers collected forty-five fluid smears of patients with previously-determined diagnoses, verified with immunohistochemical and pathological analysis. 14 of these smears represented a diagnosis of a benign effusion, 14 represented a metastatic invasion of the pleura from a distant cancer and 17 indicated malignant pleural mesothelioma. They enrolled seventeen doctors to interpret the results: nine were considered pathology experts and eight were pathology residents. They were instructed to determine if the smear indicated a benign or a malignant condition, and then, if the condition was malignant, to indicate if the malignancy was a primary mesothelioma or another metastatic cancer. After a period of five months, the nine experts re-evaluated their original results, but with the identification information stripped from those cases so they had to re-examine their own findings without reference to their original conclusions.

Results

The pathology experts had the highest overall accuracy rate for diagnosing a benign condition from a malignant one. They were able to accurately make the determination in more than 80% of the cases. Residents were able to make the diagnosis in about 71% of the cases. While inaccuracies did occur, the overall results for both figures indicate that cytological analysis of fluid smears is acceptable for a differentiation between benign conditions and malignant ones. However, the same cannot be said for its ability to differentiate between individual malignancies. When the doctors were asked to determine if the cancer was a primary mesothelioma or was cancer metastatic from a distant location, they were unable to do so with clinical accuracy. The experts again scored higher than the residents, but the overall results were still low for diagnostic purposes.

Conclusion

The researchers have concluded that their study establishes that cytological analysis alone is able to differentiate between a malignancy and a benign condition, but that further specification is impossible using this method. To be able to differentiate between primary malignancies, a doctor should employ a fine needle aspiration or a tissue biopsy.

Labels: mesothelioma

Source: Seattle Post-Intelligencer

ADAO Press Release: Asbestos Disease Awareness Organization Releases Findings that Reveal Evidence of Asbestos in Everyday Products

The Seattle Post Intelligencer is running a story on the discovery of asbestos in a variety of children's toys and other household products. The Asbestos Disease Awareness Organization, a volunteer organization dedicated to increasing awareness regarding the dangers of asbestos, funded an 18-month study that contracted with government-certified laboratories to conduct health and safety analysis on a variety of products.

The results were very disappointing.

The ADAO study found that asbestos was present in many more products than was previously realized. Among the more distressing findings was that a very popular children's toy, the "CSI Fingerprint Examination Kit," tested positive for asbestos. The game includes a number of toy tools and some fine powder that children can use to "examine" fingerprints. The laboratory found two different types of asbestos in the power. ADAO and physicians asked about the game are especially concerned that children playing with the powder will be breathing in asbestos fibers.

Other products implicated in the study included: children's play clay, powdered cleanser, roof sealers, duct tapes, window glazing and spackling paste. The tests were conducted by MVA Scientific Consultants, Inc., and Bureau Veritas North America, Inc.

The U.S. Senate has recently passed a bill aimed at banning all products that contain more than 1% asbestos. The House is expected to hold hearings on a bill that would seek a total ban.

Labels: asbestos