Respiratory Surgery Disease: Primary Lung (Pulmonary) Cancer

• Higher fatal rate among the cancer disease.
• Broadly divided into small-cell lung cancer and non-small cell lung cancer.
• It is important to find at early stage with having less symptoms.
• Final diagnose is made by pathological examination.
• Several examinations to decide therapeutic principle.
• Select treatment method from disease period and tissue type.
• Risk for lung cancer may decrease by few years non-smoking for cigarette smoker.

Higher fatal rate among the cancer disease.

Now, it is said that one out of two Japanese may develop some kind of cancer, and one out of three may die for cancer. Among of them, both disease prevalence (proportion of cancer boost people) and fatality rate (proportion of cancer boosted death) of lung cancer is in increasing tendency, and they are higher than other cancer. (Fig.1)

Fig.1: Cancer Crude Death Rate, Ministry of Health, Labor and Welfare / Current Population Survey (2008)

General public are more likely to perceive lung cancer as smoker’s disease. In fact, it becomes apparent that the risk of lung cancer development by smoking becomes higher by 4.4 times for male and 3.9 times for female, also risk of lung cancer development becomes higher from breathing (passive inhalation of cigarette smoke) of smoke (side stream smoke) flows around atmosphere. But even for the person who do not smoke, cancer may be developed, so that several researches are pushed forward currently in the area of gene abnormality etc.

Broadly divided into small-cell lung cancer and non-small cell lung cancer.

Lung cancer is broadly divided into small-cell lung cancer and non-small cell lung cancer by the tissues (kinds of cancer cell). Non-small cell cancer is further divided into glandular, epidermoid, large cell or other cancer (Chart 1). Since the most appropriate treatment method is different depend on tissue type, when lung cancer is once diagnosed, it is necessary to conduct cytodiagnosis or tissue examination.

	Tissue Type	Characteristics
Small-Cell Lung Cancer	Small-Cell Lung Cancer	Relation with smoking is large May metastasize at early stage
Non-small Cell Lung Cancer	Glandular Cancer	May be developed even for female or non-smoker
	Epidermoid Cancer	Relation with smoking is large
	Large Cell Cancer	Advancement is fast hence anti-cancer drug is difficult to affect

Chart 1: Tissue Type and characteristics of Lung Cancer

It is important to find at early stage with having less symptoms.

Prolonged cough, blood mixed sputum (blood-stained sputum), hoarse voice (hoarseness), get out of breath and pain in chest are the symptoms of lung cancer, but these are merely developed at early stage of lung cancer, hence in case if these symptoms appears out lung cancer is likely much advanced already. Because of this, it becomes very important to detect at early stage in order to cure lung cancer. Fig. 2 shows the data from certain medical organization. Many of lung cancer detected at health check (graph on top) are relatively at early stage, but on the contrary, cancers detected at the examination of the hospital and having apparent subjective symptoms (graph in the middle) are likely at advanced stage. Also, it is able to understand that there are quite numbers of people who is found lung cancer when visited hospital for another disease (graph at bottom).

Fig.2: Lung Cancer discovery momentum and stage advancement

Final diagnose is made by pathological examination.

For the diagnosis of lung cancer, image examination like X-ray and CT are the essential examination. But it is unable to say neither one of, “this is 100% lung cancer.” or “this is 100% not cancer, relax and feel comfortable.” Also, the most appropriate treatment method cannot be decided unless tissue type is identified, as mentioned later on. Therefore, in case when cancer is found suspicious by image examination, pathological examination becomes necessary with harvesting tissues or cells then check with/without cancer cell. There are several ways to harvest tissues or cells, but merit or demerit also exists in each method, so that best suitable method is selected based on the patient’s disease status.

	Merit	Demerit
Sputum Cytology	No stress for body	Detection rate is low
Bronchoscope (Bronchial Camera)	Adopted for Central Lung Cancer Detection Rate is somewhat higher	Detection Rate is somewhat higher Complicated disease like pneumothorax or respiratory tract hemorrhage
CT guided Biopsy under pulmonary	Adopted for peripheral lung cancer Detection rate is high	Difficult for Central Lung Cancer Complicated disease like pneumothorax or aeroembolism
Thoracoscopic Surgery	Thoracoscopic Surgery Able to combine treatment Able to combine treatment	Necessary to have general anesthesia(large invasion)

Chart 2: Method for tissue/cell diagnosis of Lung Cancer

Please refer The Japan Society for Respiratory Endoscopy homepage http://www.jsre.org/qa.html for bronchoscope.

Several examinations to decide therapeutic principle.

When diagnosed as lung cancer at pathological examination, first diagnose the degree of progression (disease period, stage), then based on them, conduct the following tests to decide treatment principle.

Tumor Marker

There are multiple tumor markers, such as CEA, SCC antigen, CYFRA, Pro-GRP, NSE, available for lung cancer. Tumor marker which turns into abnormal one is different from the tissue type. When disease is progressed, most of tumor marker are likely increased. Even if it is an advanced cancer, there is a case where tumor marker is normal. On the contrary, tumor marker shows abnormal even if it is not a cancer, so that it is not used for diagnosis or to determine therapeutic principle. Trends in disease is evaluated by the examination before, under, or after the treatment.

CT Examination

Check the size of lesion or level of proliferation. It is able to evaluate exist/non-exist of metastasis to lymph node or other organs, hence it is inevitable for advancement diagnosis.

Brain MRI Examination

Examine existence/non-existence of metastasis to the brain. Contrast examination is expected.

Bone Scintigraphy

Examine existence/non-existence of metastasis to bone. It is necessary to pay attention for confusion as metastasis if having recent bone fracture.

PET-CT Examination

Check the cancer proliferation to entire body. It is necessary to pay attention for confusion as metastasis if having an inflammation.

Others

When principle is determined for proceeding the surgery, it is evaluated by echocardiography or respiratory function test whether or not patient is able to endure surgical operation.

As an aside, in Japan, chest X-ray test is conducting at medical checkup in order for earlier discovery of lung cancer. Sputum examination is added for smoker. But as they are low in detection rate so that there are quite a lot of cases where cancer has already advanced when it is found. Now, opportunistic screening using chest CT examination becomes common broadly so that early stage lung cancer is likely found. In the large-scale research using CT examination targeting for heavy smoker in the USA, it is found that early detection reduces not only mortality risk by lung cancer but also fatality rate with all cause of death. (There is a negative opinion saying that useless surgery is conducted because the shadow which is not a cancer one is diagnosed as lung cancer.) Therefore, in western countries, instead of conducting chest X-ray examination, it becomes standard procedure to diagnose with using CT examination.

Select treatment method from disease period and tissue type.

Treatment method for lung cancer may vary depend on the progress of disease (stage) and tissue type.

Surgical Operation

Surgical operation is the primary selection (Surgery is conducted for stage I small cell lung cancer, but unlike non-small cell lung cancer, postsurgical chemotherapy is requested.) in order to aspire for complete cure by surgery for stage I/II non-small cell lung cancer.

Surgical method is; open chest surgery and thoracoscopic surgery are conducted from approach point of view, and largely divided into complete removal of one whole lung, lung lobectomy, segmental resection and partial ablation from the aspect of lung resection amount. Also, there is a case where lymph node dissection is conducted, or a case it is not conducted. As for the separation of open chest surgery and thoracoscopic surgery, it is individually decided depends on facility’s operational principle, surgical doctor’s skill and experience, patients’ symptoms (progress of lung cancer, surgical history for lung, and basic disease). And as for the lung resection amount and existence/ non-existence of lymph node dissection, it is decided with comprehensive checkup of progress level of lung cancer and patient’s lung condition, etc., in order not to decline radicalness of lung cancer and also not to decrease postsurgical breathing function as much as possible.

For stage IIIA non-small cell lung cancer, cases are mixed with the case where surgery is must and where surgery should not be conducted, hence it can’t be completely explained. Whether or not surgery is conducted is decided from disease diffuse condition.

Chemotherapy (Anti-cancer agent therapy)

This is a treatment to kill cancer cells with drip infusion (or take orally) of anti-cancer agent. Cancer is getting large by gene broken abnormal cell is actively grow proliferously. Anti-cancer agent has the effect to suppress cell cleavage, but it also suppresses normal cell cleavage so that as a result, it raises “side effects”. Hairy root, mucosal membrane of from mouth to bowel, bone marrow producing cells in the blood are the active cell cleavage organs (or tissues) in the body. Because these organs (tissues) are damaged by anti-cancer agent, it develops side effects, such as “dehairing”, “nausea”, “diarrhea”, “bone-marrow suppression (such as neutrophil depletion, anemia, platelet depletion)”. (Depend on the kind of anti-cancer agent, developed side effect may vary). Furthermore, Surgical operation or radiation treatment is able to treat at site, but anti-cancer agent is affecting to entire body so that it is effective even if disease spreads around the entire body. Hospitalized treatment or visiting treatment is decided depends on kinds of medicine or patient’s condition.

Recently, it is clarifying that abnormal gene develops lung cancer so that treatment drug is under the development in targeting such abnormal gene. A part of these drug shows the dramatic effects, but on the other hand, it has an issue of “resistance characteristics; lose effect someday”, so that research is under way for diagnosis and treatment drugs to overcome “resistance characteristics”.

Also, new immune treatment method, to kill cancer cell by reactivating immune cell, which function has been declined by cancer cell, is under way. At the end of year 2005, “Opdivo” has been introduced in Japan so that lung cancer treatment has been greatly switching.

Radiation Therapy

Radiation therapy is the treatment which high-energy radial ray is send to the cancer area to kill cancer cell. Because some level of radial ray is applied to the cancer tissue surrounding organs, this may result as side effects. Because of side effect to the entire body are less so that surgical operation is desired in nature in considering the symptom, the person who do not have enough strength for surgical operation, may have radiation therapy with aiming the complete cure. Or, “combined modality therapy” , which make the complete curing possibility higher with combining radiation therapy with chemotherapy or surgical operation, can be conducted.

In case when symptoms appear due to blood vessel or nerve is pressed by cancer, applying radial ray to particular part makes symptom lighter while pressed cancer is getting smaller by radiation. Furthermore, this therapy may ease the pain occur by cancer metastasizes to bone, or there is a case where it may prevent to become inconveniences by the possible bone fracture for future due to metastasis to backbone. Also, in case cancer is metastasized to the brain, surgical operation is conducted, but when surgery is difficult case, it is treated by radial ray application.

Palliative Therapy

For high-aged person, person who is assumed as inability of endurance for aforementioned therapy fundamentally by some kind of other disease already be onset, or person who do not wish to have “cure the cancer” treatment or “extending life expectancy”, possible lung cancer symptoms (pain or breathless) can be palliated by pain relief medication or oxygen breathing. While patients may handle with the disease well, oppressive disease symptoms are relieved so that patient can have better end. That is palliative therapy.

Risk for lung cancer may decrease by few years non-smoking for cigarette smoker.

Regarding to the preventive method for lung cancer, “smoking cessation” is the only one which is proved effective. (Fig.3). As mentioned before, cigarette smoking elevates the risk of lung cancer development by 4.4 times for male and 3.9 times for female. Even for non-smoker, risk is elevated by 1.3 times with inhaling (passive exposure to tobacco smoke) flow around smoke of cigarette (side-stream smoke).

	All cancers	Lung Cancer		All cancers	Lung Cancer
Smoking cessation	Assured	Assured	Soy bean		？
Alcoholic Drink	Assured	？	Assured		？
Obesity	？	？	Dairy products	？	？
Exercise	？	？	Green Tea	？
Infection Disease		Up by Pulmonary Phthisis	Coffee
Vegetables	？	？	Isoflavone	？	？
Fruits	？	Possible	Vitamin E	？	×？
Mea	？	？	β-Carotene	？	×

Fig. 3 Effectiveness of preventive method for lung cancer

When smoking, nicotine effects to brain in approximately 7 seconds. Nicotine will temporary attend to the spirit and improves motor nerve function and awaken brain consciousness, on the other hand, it makes the spirit feeling relaxed. But these “good effect” may lose in few minutes. Therefore, body is going to require next nicotine and if not, abstinence symptom, like irritation, may come up. (nicotine dependence)

When smoking, nicotine effects to brain in approximately 7 seconds. Nicotine will temporary attend to the spirit and improves motor nerve function and awaken brain consciousness, on the other hand, it makes the spirit feeling relaxed. But these “good effect” may lose in few minutes. Therefore, body is going to require next nicotine and if not, abstinence symptom, like irritation, may come up. (nicotine dependence)

Fig. 4: Several Health Improvement Effects appears after the smoking cessation.
(England Tobacco White Paper “Smoking Kills”, 1998 / IARC Cancer Prevention Handbook Volume 11, 2007)

When smoking, nicotine effects to brain in approximately 7 seconds. Nicotine will temporary attend to the spirit and improves motor nerve function and awaken brain consciousness, on the other hand, it makes the spirit feeling relaxed. But these “good effect” may lose in few minutes. Therefore, body is going to require next nicotine and if not, abstinence symptom, like irritation, may come up. (nicotine dependence)

Fig. 5: Risk decrement for lung cancer by tobacco cessation