Breathing and lung cancer

How does lung cancer develop? Like the other cancers that we have discussed so far, lung cancer does not develop in a day. Lung cancer is a common adulthood cancer. It is lifestyle-related because of its intimate relations with breathing. Lung cancer is, therefore, extremely rare in children. So, this means that the development of lung cancer is closely associated with substances in the air we breathe in.

Is the air the same all over the world? The air is probably very different in various places of the world. I think you would agree with this. We have an earnest desire to protect the natural environment of the Earth. We have already seen phenomena that would have a devastating impact on the livelihoods of future generations, unless improvements are made. Air cleanliness in urban and rural areas may considerably differ in terms of concentrations of exhaust fumes.

Pollen and dust concentrations may be remarkably higher in rural areas. Forests are known to have a special smell that reduces fatigue. We now have a fairly complete understanding of the types of substances in exhaust gases that are associated with lung cancer.

Basically, these substances are chemically related to oxygen and nitrogen which are the main constituents of air. More specifically, I’m referring to the reactive oxygen species, the “bad” type of oxygen. Nitrogen has a reactive form as well. Reactive nitrogen is found in exhaust fumes. The carcinogenic substances found in tobacco tar are basically clusters of reactive oxygen species; I shall come back to this point later.

Air passage

The air passage from the mouth or nose to the lungs consists of branching tubes, and somewhat resembles a cave. These branching tubes are called respiratory tracts, or airways, because these paths are where air travels back and forth. Air passes through to the lungs, allowing oxygen to enter body, and carbon dioxide to leave the body.

Inside the lungs, the bronchi branch out into bronchial trees, continued by narrower branches called bronchioles, and at the end, there are many alveoli (sacs filled with air), which are shaped like a bunch of grapes. The lungs are located in the chest, on either side of the heart. The lungs can expand when the pressure in the chest cavity is lower than the pressure in the air outside. The lungs inflate and deflate each time you breathe. The weight of the right lung is about 250 grams, and the left lung is about 200 grams. The lung is a light-pink, air-filled organ that is relatively light for its volume.

Glandular cells and ciliated cells

Considering the structures from bronchi to the alveoli as one unit, the right lung is divided into three sections called the upper, middle, and inferior lobes, while the left lung is divided into two sections. The internal walls of these bronchi and alveoli are lined with several types of epithelial cells. The bronchial epithelial cells consist of ciliated epithelial cells (which have fine hairs on the surface), columnar epithelial cells, and goblet cells (which secrete sticky liquid). The epithelium of the alveoli consists of two types of cells: alveolar type I cells and alveolar type II cells. These are called glandular cells, and these cells may develop into adenocarcinoma of the lung, a type of lung cancer.

The cilia in the ciliated epithelium move in a powerful wave-like motion from the back of the bronchi towards the direction of the mouth. This movement removes foreign materials that have entered into the deep areas of the bronchi (when air is breathed in) through the production of phlegm. The foreign materials in the air are of varying sizes, and while the larger materials like pollen get stuck on the hairs in the nose, the smaller materials can travel to the far end of the lungs.

Exhaust fumes, tobacco smoke, and asbestos (traditional materials used for brake linings and heat insulation) are microparticles that float in the air, which means they can enter deep into the lungs. When foreign materials enter the alveoli where no cilia are present, it would no longer be possible to remove them.

There has been an interesting experiment conducted with ciliated epithelia cells. In this experiment, these cells were cultured in a special plate, and positioned so that the cilia were moving in a fixed direction. The movements of the cilia rapidly decreased when water-soluble substances from tobacco smoke or nicotine were added to the culture solution.

Such changes are predicted to occur in the epithelial cells of the bronchi of smokers. It is widely known that metaplasia also occurs-this is where ciliated epithelial cells are replaced by nonciliated epithelial cells. When this happens, foreign materials accumulate in the mucous membrane of the respiratory tract and cause inflammation. The carcinogenic effects of foreign materials and the reactive oxygen produced by local inflammation of cells can lead to the destruction of epithelial cells and cause damage to DNA associated with the regeneration of cells.

When this process occurs continuously during a latency period, abnormalities occur in the genes that promote cell growth (accelerators), in the genes that inhibit cell growth (brakes), or in the genes that cause programmed cell death (apoptosis), leading to cancerous changes in the epithelial cells.

Equally important as ciliated cells is a rich supply of immune cells (which trigger immune responses) in the respiratory tract mucosa. They are known as white blood cells. These cells are associated with chronic inflammation, and are thus closely associated with diseases such as allergies and asthma. They also trigger inflammation associated with tobacco and exhaust fumes, and are a major factor in the onset of cancer. BioBran can properly regulate these immune responses. Experiments on animals have indicated that it may be effective in alleviating symptoms of hay fever and asthma.

Mass production of cigarettes and the outbreak of lung cancer

The dissemination of the cigarette that led to its widespread use as we see today started in the beginning of the 20th century. Back in those times, lung cancer was very rare. Lung cancer was thought to be a rare cancer that occurred in animals under experimental conditions, and it was believed that it only occurred when special carcinogens were administered to these animals to trigger its onset. Compared to the days where people were puffing on a pipe, the amount of tar intake rapidly increased with the spread of cigarette smoking. This shift towards cigarette smoking occurred due to the development of automated machinery for the production of cigarettes.

It is a well-known fact that, in the 20th century USA, the rising curves of cigarette consumption and mortality rates are interrelated with a 20-year difference. In Japan, this trend occurred together with improvements in the economic situation after World War II. Moreover, the trend closely resembles the ways of which lung cancer is currently rising in countries in Eastern Europe and Africa.

Today, smoking not only increases the risk of lung cancer but also of other cancers such as cancers of the respiratory tract, breast, digestive tract, pancreas, and bladder. The tar in cigarettes is absorbed into the body and circulates around the entire body. When substances in tar are excreted into urine, they will remain in the bladder for some time and affect the epithelial cells of the bladder during this time.

Unfortunately, secondhand smoking also increases the risk of cancer in people who are near smokers. Smokers often show symptoms of mild chronic bronchitis. Symptoms such as dry cough and increased phlegm frequently manifest. Complications such as lung fibrosis (idiopathic interstitial pneumonia) and emphysema arise. People with lung fibrosis have a high susceptibility to developing lung cancer, which is evidence that chronic inflammation stimulates the onset of cancer.

The toxic substances that enter the body damage the intravascular cells (cells inside blood vessels) due to the production of reactive oxygen species. This leads to local inflammation or the formation of blood clots. Smoking is also a factor in arteriosclerosis, and is intimately associated with angina pectoris and myocardial infarction, as well as cerebrovascular disease. Therefore, it is not an overstatement to say that tobacco smoking is associated with an increased risk of almost all types of lifestyle-related diseases.

Based on the knowledge that has been acquired through medical evidence, it is a major problem that the insurance premiums are the same for smokers and non-smokers. In North America, many insurance companies have different premiums for smokers and non-smokers. In the United States, tobacco companies have often lost lawsuits filed against them for the damage to health caused by cigarettes.

Awareness of the risk of lung cancer

The first step towards the prevention of cancer and lifestyle-related diseases is for smokers and passive smokers to do a self-assessment of their risk of cancer, and to become aware that they are at high risk. People who are in close contact with exhaust fumes are not only exposed to polyaromatic hydrocarbons, which are carcinogens similar to tobacco tar, but are also exposed to asbestos used in car brakes.

Therefore, people who work in the automobile industry should be aware that they are at high risk of developing lung cancer and pleural mesothelioma (a malignant tumor that develops in the mesothelial cells, which are cells that cover the surface of the lung and thoracic cavity). Pleural mesothelioma is a malignant tumor that is particularly difficult to cure. That is why it is necessary to upgrade from the usual chest X-ray and take a chest CT scan every few years.

Extra-early detection of lung cancer

For a long time, chest X-ray was a part of lung cancer screening, and its use was aimed at early detection of lung cancer. However, the detection rate is low, and it is becoming evident that in many cases, the cancer is no longer in its early stages by the time it gets detected. This information is based not on my own judgment, but on recent information from various academic papers.

Studies conducted in Japan have shown that chest X-rays were effective for the early detection of lung cancer, but the study results did not show that they were remarkably effective. The problems of X-ray image (radiogram) interpretation lay in the backdrop of this situation. The doctor’s skill level has a large influence on the interpretation of radiograms, which means that there is a possibility that some cancerous changes may go undetected depending on the doctor in charge of the diagnosis. In actual fact, lung cancer mortality rates have not improved despite the widespread use of chest X-ray exams.

It has been pointed out that the outcomes after surgery for the smallest lung cancer found on X-ray exams is evidently worse than the outcomes after surgery for early stage lung cancer found in CT (computed tomography) scans. In both Japan and America, the statistics reveal a grave situation; the prevalence rate and mortality rate are hardly different for lung cancer.

What this means is that the preventive measures and treatments performed for lung cancer in the past up until the present have been very ineffective, indicating the urgent need for improvements in these areas. In fact, the medical checkups for employees organized annually by companies have not necessarily contributed to the early detection (i.e., the detection of tumors while they are still very small and treatable) of lung cancer, Wide availability of a test with a higher sensitivity than chest X-ray exams is urgently required.

The current reality in most medical institutions is that if lung cancer is suspected, a chest X-ray is used for screening and confirmation. If no abnormalities are found at this stage, CT scans will not be performed.

Recently in Japan, several institutions have presented initial data on lung CT scan screening. CT scans were performed in studies involving 2,000 to over 10,000 Japanese people aged 50 years and above (details such as age composition, male to female ratio are unknown). Abnormalities were detected in 3 to 6 people out of every 1,000 people. Unfortunately, not all of them were lung cancers in early stages; some of them had already advanced to later stages. As you can see, the sensitivity of chest X-rays is not ideal for detecting early stage cancer that is still treatable.

It is hoped that high-sensitivity CT scans and PET (positron emission tomography) scans will help screen for early stage lung cancer. These advanced technologies can generate 3D images of the lung (akin to computer graphic images) using a series of sectional images, and these images can be taken in just 10 seconds or so, while holding one’s breath. The amount of radiation exposure has been reduced to the lowest possible level. At the Fujimoto Hayasuzu Hospital (Head: Toshiro Fujimoto), a hospital in Miyazaki prefecture, integrating the use of PET scans, CyberKnife and Gamma Knife has allowed them to steadily improve their outcomes.

Early stage lung cancer caused by smoking generally grows slowly, so if your first CT scan or PET scan shows no abnormalities, you can be rest assured for at least 4 or 5 years after that. If you take these tests, I recommend that you ask for a copy of the test images and report of the findings. These documents are official documents, like a personal history of health, and they will be very important when obtaining a second opinion.

Surgical treatment

These days, many cases of early stage lung cancer can be treated by limited surgery without requiring open chest surgery. In this surgery, local anesthesia is administered to the intercostal space (the space between ribs) closest to the tumor, and several small opening are made around this area. While looking through a thoracoscope, surgical equipment is used to remove the area of the lung with the tumor, and the area is sewn back together with a device to ensure that air does not leak through.

Tumors often recur in heavy smokers, so thoracoscopic surgery is useful for finding and removing such tumors while they are small, and in their earlier stages. If the cancer is limited to one lobe of the lung, it is possible to remove just that lobe (lobectomy). When the cancer is spread across different lobes, it will be necessary to remove the entire lung on one side, which is a major surgery.

Pathological diagnosis of lung cancer

Lung tissues that are removed during surgery are usually preserved in formalin and chemically processed (fixation). As the lung is inflated in its original state, keeping it inflated makes it easier to conduct tests and analyses. Therefore, a needle is inserted at various points of the removed tissue and formalin is injected into these points to inflate the lung tissue before fixing it.

The formalin-fixed lung tissue is analyzed by a pathologist, and is processed into a form that facilitates examination. The samples of lung tissue, which have been resized into an appropriate size for microscopic examination, are processed in several stages using various chemicals and embedded in paraffin.

Using a microtone (a mechanical device for slicing specimens, and which has a knife that can be adjusted by increments of 1/1,000 mm), the lung tissue embedded in paraffin can be made into thin slices with a thickness of several microns. In fact, the resulting lung tissue slices are thinner than the Somei Yoshino cherry blossom petals.

These slices are spread onto glass slides. The tissue and cells are stained using several different dyes, and examined under a microscope. The pathologist examines the sample, checking the type of cancer and the surrounding lung tissues. The pathologist’s report states the patterns of growth of the cancer, whether the cancer has been completely removed, whether the cancer has spread to lymph nodes, veins, and the surface of the pleura, or whether it has metastasized to any lymph nodes.

Lung cancer and anticancer agents

There are two major types of lung cancer: small-cell lung cancer and non-small-cell lung cancer. Treatment methods vary depending on which type of lung cancer patients have. Non-small-cell lung cancer is a particularly malignant cancer; anticancer agents have very little effect on this type of cancer. Some anticancer agents exert their effects on the nucleus or DNA, while other anticancer agents, such as Iressa, have an effect on cell-surface molecules involved in cell proliferation.

The similarity between these two types of anticancer agents is that both function to suppress the proliferation of cells. Among the different types of lung cancers, adenocarcinoma is the most difficult to treat using anticancer agents. The pharmaceutical company that developed Iressa publicly announced that Iressa was not effective in lung cancer. On the contrary, the Ministry of Health Labour and Welfare in Japan appears to acknowledge Iressa’s effectiveness in lung cancer. However, their viewpoint remains unclear due to the lack of scientific evidence.

Sputum cytology

Screening for lung cancer includes a test category called sputum cytology. This is a test that examines cells in sputum. Cells from the respiratory tract or lungs can break off together with secretions from these areas, and these cells can be found in sputum. The laboratory technician for sputum cytology and a team of pathologists determine whether the cells are healthy or not.

Sputum cytology complements the weaknesses of CT scans. Computed tomography (CT) generates three-dimensional images using a series of X-ray images. CT scans can be used to visualize very small masses inside the lung, bronchi, and bronchial walls, and are known to be particularly effective for detecting changes inside the lung. However, it is considered difficult for CT scans to detect early stage bronchial cancer because this type of cancer spreads thinly on the mucosal surface of large respiratory tracts.

In this case, it is useful to use sputum cytology, which microscopically examines the atypical epithelial cells that have broken off from the mucosal surface. It is necessary to examine sputum coughed up on three consecutive days, rather than just one day.

Food and lung cancer prevention

As I have mentioned earlier, the latency period of 10 or more years leading up to lung cancer can be thought of as a period for preventing cancer. It is not a bad idea to rely on food and good quality supplements as a means of reducing the amount of reactive oxygen produced in the body. Reducing chronic inflammation of the respiratory tracts is required for the prevention of factors that promote cancer, based on scientific evidence.

Certain foods have antioxidant effects. Fruits are especially recommended as they have various beneficial effects. In a recent, internationally-acknowledged epidemiological study, researchers found that fruits were effective, although they did not identify a specific fruit to be particularly effective.

In contrast, the effectiveness of vegetables was unclear in this study. We can only anticipate that there are benefits of antioxidants contained in vegetables. We are also hoping to find detoxification and enzyme effects of garlic, curry spices (e.g., turmeric), natural pigments in dark colored vegetables (such as carotene, and xanthine), and trace metals such as selenium and zinc.

BioBran is a supplement that has been found to have antioxidant and anti-inflammatory effects, and it has also been shown to be effective in alleviating the adverse effects that arise from treatments with anticancer agents. I believe that the supplement may be worth trying, not only for lung cancer but for all types of adulthood cancers.

In the next article, I will be discussing strategies for the treatment and prevention of breast cancer.