Identification of Asbestos

Over the years much data have been accumulated about asbestos, which suggests that amphibole asbestos and its nonasbestos analogues possess very different biologic potential. Davis et al demonstrated that although asbestiform tremolite was extremely carcinogenic when
injected into peritoneal cavities of rats, nonasbestiform tremolite samples had little or no carcinogenic potential. Therefore, it is important to distinguish between asbestiform and nonasbestiform amphiboles and types of fibers in bulk, air, and tissue samples. There are some
problems related to the mineralogic techniques necessary to prepare and characterize samples. The designation of the shape and size of fibrous materials can be relatively easily revealed by optical examination. Optics became the technique of choice to investigate the occurrence of inorganic fibrous airborne particulates at occupational sites, in schools, or any buildings, and even outdoors where filters could be set up to obtain a representative aliquot of the air. However, the light (optical) microscope does not have enough spatial resolution and so is not sufficient on its own for positive identification of minerals. It is difficult to identify some fibers such as chrysotile in the tissue samples under the optical microscope because of the small fiber sizes. Since the small fiber size of chrysotile in the tissue samples preclude the use of optical microscopes, morphologic, chemical, and structural identifications are done by combinations of methods in order to makeunambiguous mineral identifications. The crystal chemical range of potentially hazardous inorganic and mineral species should be accurately identified. Morphologic identifications can be performed by using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Chemical information is most commonly obtained by energy dispersive spectroscopy (EDS) or wavelength dispersive spectroscopy (WDS), which is an integral part of SEM or TEM. A relative error percentage for EDS is about 10% and for WDS is about 1%. Therefore, EDS provides only semiquantitative information, but WDS provides more quantitative information on chemical composition of the
sample. Crystal structures can be determined by electron diffraction (ED) on samples. Powder x-ray diffraction (XRD) is a powerful technique providing that enough material is available, but not for a mineral present at low percentage in tissue and air samples. Certain regulations may require specific species of amphiboles; thus, quantitative chemical data may be necessary. For example, substitution solid solution series of amphiboles, such as a tremolite and an actinolite, must be identified. The SEM studies combined with EDS may not be conclusive because of the lack of information on the mineral structure. It is also very difficult to observe chrysotile through the electron microscope because of its beam sensitivity. Analysts tend to measure fibers that are more stable under beam conditions. Lung burden studies indicate that chrysotile is often inhaled as a shorter fiber than amphiboles. Therefore, in a tissue with both amphibole and chrysotile, it is possible to make a misjudgment unless the fibers are identified individually. 

The levels of sensitivity using the high-resolution techniques now available mandate that we follow up the reactions delineated as interference of inorganic materials in the biologic environment. The information on the inorganic fibrous particulates can be matched with the equally high-resolution techniques applied to analyses of tissues, with data gathered at the cellular and molecular levels. The advances in techniques increase the possibilities that we can test hypotheses and, it is hoped, gain greater understanding from the anatomic to the genetic
of the reactions that lead to induction of disease. Coordinating ultramicroscopic levels with the health and mineralogic investigations for a particular geographic area should enable us to refine the possibilities. The exchange of information among the several disciplines is needed to advance our knowledge.

Mesothelioma and Asbestos Exposure

It was the Conference on the Biological Effects of Asbestos at the New York Academy of Sciences, organized by Irving Selikoff in November 1964 , that put both mesothelioma and asbestos on the map. Before that meeting, few people in the scientific or general community had much knowledge of either subject. There they learned the nature and numerous essential industrial uses of a group of naturally occurring mineral fibers, collectively known as asbestos, although in fact comprising at least five distinct materials, chemically, physically, and geologically. Of these, chrysotile, a serpentine mineral mined mainly in Quebec and the Ural mountains of Russia, made up over 90%. Of the remainder the two most important were crocidolite and amosite, produced mainly in South Africa and Australia, both amphibole minerals with distinctive qualities valuable for heat insulation, naval marine use, and the production of large-bore cement pipes. Two other amphibole mineral fibers were anthophyllite, of limited production in Finland, and tremolite, little used, though by far the most widespread
geologically. Presenters at the conference stated that within some 20 years of the first industrial exploitation of asbestos in the 1880s, workers heavily exposed to airborne fiber and dust developed a distinctive, seriously disabling and sometimes fatal diffuse pulmonary fibrosis, later termed asbestosis. Little was done to limit exposure until the late 1930s, when after a well-conducted survey of four asbestos textile plants in North Carolina, Dreessen et al (2) and others of the U.S. Public Health Service recommended in 1938 that a workplace dust concentration of 5 million particles per cubic foot (about 15 fibers/mL) should not be exceeded. Mainly because of the Second World War, this recommendation was not implemented; and probably for the same reason it went unnoticed that there were case reports by some German
pathologists of malignant tumors of the pleura and peritoneum in men with asbestosis. Thus it was only in the 1950s that the causal association of asbestos exposure with lung cancer in the United Kingdom, and later with mesothelioma in South Africa , was recognized.

Until that time even the very existence of primary malignancies of the mesotheleum was questioned by reputable pathologists. Looking back, however, a review by Saccone and Coblenz in 1943 had included the identification of over 40 cases in autopsies published since 1870, and referred to two cases of “endothelioma” reported in 1767 by Lieutaud in France among 3000 autopsies. That mesothelial cancers in low frequency probably occurred well before the industrial use of asbestos is discussed more fully later. Indeed, a low background incidence of unknown etiology has almost certainly continued, affecting both children and adults.

Chemoradiation In Cancer Therapy

Chemoradiation In Cancer Therapy

The medical uses of ionizing radiation have expanded dramatically since Wilhelm Roentgen first discovered it at the end of the last century. In particular, it has proven to be an effective agent in the ongoing battle against cancer. It is presumed that the essential target for radiation is cellular DNA where it acts through the formation of free radicals to directly or indirectly cause double-stranded breaks. It is these doublestranded breaks in the DNA that are felt to be the lethal lesion that malignant cells sustain from therapeutic radiation.

It was in the period of World War II that it was possible to induce lasting remissions

and potential cures of hematological malignancies with nitrogen mustard (1), which was

really the first chemotherapeutic agent put to widespread use in the treatment of malignant

disease. Since that time, a multitude of other drugs have come and gone in the search

for a cure. A few drugs appear to have found a more lasting place in the therapeutic

armamentarium, including doxorubicin, cisplatinum, cyclophosphamide, and 5-fluorouracil.

A new generation of drugs with varied mechanisms of action has appeared in

the last decade and also has the potential to remain as key in the treatment of cancers.

These agents include paclitaxel, docetaxel, gemcitabine, irinotecan, and vinorelbine.

Although oncologists and researchers have often tried to cure cancers with radiation

alone or with various chemotherapeutic strategies, in general these have been met with

limited success for any number of reasons, which will be outlined below. The strategy of

integrating different treatment modalities into a more comprehensive approach to both

local control and the treatment of micrometastatic disease, often referred to as combined

modality therapy, has been met with some success. Although the delivery of neoadjuvant

and adjuvant chemotherapy may contribute to improved local control, it is less clearly

demonstrable than with concurrent therapy. This chapter will focus on combined modality

therapy with an emphasis on concurrent chemoradiation. It will attempt to set the

background with an examination of the rationale and the difficulties that are inherent with

concurrent therapy from the point of view of both the delivery of radiation and of chemotherapy.

Beyond this it will illustrate some of the gains achieved in therapy using a

concurrent treatment approach. Finally it will focus on the potential for the future that lies

in an increased understanding of the molecular players in neoplastic processes as well as

the response of malignant cells to therapy with radiation and chemotherapy. The integration

of new agents that are aimed against more specific cellular targets than either

radiation or traditional cytotoxic chemotherapy may significantly influence the success

of combined modality therapy in the future.

TREATMENT PARADIGMS

Surgical therapy as a sole modality often fails because micrometastatic disease is

already present at the time of surgery or because malignant cells are present beyond the

surgical margins of the resection. Radiation therapy is sometimes added before or after

surgical resection to decrease the possibility of local recurrence when it is felt that there

is a high enough probability of residual malignant cells being present after surgery.

However, radiation therapy as both a sole modality of treatment or as an adjuvant or

adjunctive therapy may fail to sterilize tumors because of micrometastases or because the

dose of radiation that can be safely delivered is limited by the tolerance of the surrounding

normal tissues. Certainly the explosion of new technology in the current computer age

has improved our ability to deliver further radiation in a more conformal fashion. However,

in those malignancies that have a high propensity for distant spread of disease,

delivery of higher doses of conformal radiation may not prove to be a satisfactory approach

to the problem. Unfortunately chemotherapy rarely proves to have a curative role on its

own in the treatment of solid tumors.

BIOLOGY COMPLICATES THE DELIVERY OF RADIATION
The delivery of therapeutic radiation is limited by the tolerance of the surrounding
normal tissues. Data have been compiled over many years that suggest which structures
are able to tolerate certain doses with acceptable amounts of toxicity (2). This model for
thinking about how to plan the delivery of radiation has changed considerably with the
advent of new computer- and automation-driven technologies that allow for the more
conformal delivery of dose to the gross tumor and to the clinical target volume. New
analytical tools called dose volume histograms, which allow for a definition of the dose
delivered to a percentage of an organ, have begun to replace more traditional concepts of
normal tissue tolerance. Although these technology-related advances allowfor the delivery of higher doses of radiation, this may only be an effective strategy in those
tumors whose biology makes them amenable to a local therapy as the sole modality of
treatment. Those tumors that have a predilection for the early dissemination of
micrometastases cannot be effectively treated by a local therapy alone. However, those
tumors that tend to remain localized for longer periods of time may have several biologic
reasons that underlie their resistance to radiation.

Tumor Hypoxia

Tumor Hypoxia

The equally intriguing phenomenon of tumor hypoxia has been documented to occur in a number of tumor types including cancers of the uterine cervix , head and neck , bladder as well as in soft tissue sarcomas . This is the result of inadequate blood supply to tissues that leads to the compromise of biological function and in the case of cancers this is usually related to abnormal or inadequate blood vessels, anemia, or the formation of methemoglobin or carboxyhemoglobin that will reduce the oxygen carrying capacity of the blood in smokers.

There have been several observations collected over the last few decades that suggest that tumor hypoxia plays a key role in outcome. These observations are as follows: tumors often have lower median partial pressures of oxygen than their tissues of origin ; the presence of tumor hypoxia cannot necessarily be reliably predicted by factors like stage, size, histology, or grade; tumor-to-tumor oxygen variability is often greater than intratumor oxygenation

differences , and recurrent tumors often are more poorly oxygenated than their corresponding primary tumor.

While the controversy about the exact role that anemia plays in determining outcome from radiation therapy is age old, i.e., big tumors bleed more and are more likely to spread vs tumors in anemic patients tend to be more hypoxic and hence more resistant to therapy, evidence is accumulating to suggest that reality is firmly rooted between both views. Radiosensitivity is known to be significantly limited when the partial pressure of oxygen is less than 25–30 mmHg.

It has been known for years that molecular oxygen will increase radiation-induced DNA damage through the formation of oxygen free radicals that act to inflict “indirect” damage beyond the “direct” effects of radiation on DNA . There is also substantial evidence obtained over the last few years that tumor hypoxia induces genomic changes with subsequent upregulation of genes that are linked to radiation resistance . Equally compelling are the experiments that have revealed that presence of tumor hypoxia is linked to an increased incidence of metastatic disease .
The microenvironmental signals in a hypoxic tumor environment are such that there is greater genomic instability and selection pressure to maintain those cells with increased angiogenic potential and decreased apoptotic potential. Improved understanding of this interesting phenomenon will ultimately lead to improved potential for therapeutic targeting of tumors.

Symptoms of mesothelioma

Symptoms of mesothelioma