Treatments and Protocols BEYOND The Traditional
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Acid Reflux -- Esophageal Spasms
Gastroesophageal Reflux Disease (GERD, Acid Reflux)
Acid-Alkaline Balance by Karl Loren
Dr. Weston Price -- On Acid -- Alkaline Balance
Mass Near The Esophagus -- Cancer? Benign?
Advice From Friends -- Esophagus Cancer
Treatments and Protocols BEYOND The Traditional
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Prospective Investigation of Tumor Markers and Risk Assessment in Early Cancer Screening
Karl Note: The DETECTION of cancer at an early stage is an important element of effective treatments. One of the reasons that detection techniques have suffered is that the US Drug Industry has controlled this area. An even bigger reason is that these newer techniques often cost much more money than standard techniques and would bust through the top of insurance coverage. Research and use of these techniques is often quite "standard" in countries where insurance does not dominate the standards of medical care.
Even when detection is no longer an issue, there are other measurements of an existing cancer which can be done with modern "markers" and help inform the patient. For instance, when a cancer is fast or slow growing it tells the patient how much time he or she may have to look for alternative forms of treatment. This type of detection is available, but not significantly in the US.
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| Background. Many researchers have reported
that tumor marker diagnosis may not be useful in the early detection of
cancer. However, the authors proposed a new diagnostic system using a tumor
marker combination assay. Methods. The authors screened an asymptomatic population (2126 subjects) in Japan for early cancer over a 2-year period (1984-1986) using this tumor marker combination assay. The serum tumor marker combination assay data were analyzed: tumor-specific tumor markers (carcinoembryonic antigen, carbohydrate 19-9, heatstable alkaline phosphatase, and tissue polypeptide antigen), tumor-associated tumor markers (ferritin, the ratio of ferritin to serum iron, immunosuppressive acidic protein, sialic acid), and growth-related tumor markers (alkaline phosphatase isoenzymes, ribonuclease). The tumor growth levels of the subjects were assessed by the tumor marker combination assay and classified into five tumor stages (Stage I, tumorfree; Stages II-III, precancer; Stage IV, preclinical cancer; Stage V, suggestive of cancer weighing over 1 g). The follow-up period was 5-7 years. Results. The percentage of subjects in tumor stages IV and V increased with age, whereas the percentage in tumor stages II and III decreased. The distribution of screenees within each tumor stage was as follows: 1, 0.1%; 11, 11.8%; III, 58.8%; IV, 24.8%; V, 4.6%. The rate of incidence of cancer for Stages V, VI, III, It and I was 29.5% (28 of 95),2.7% (14 of 528),0.7% (9 of 125110.4% (1 of 250), and 0 (0 of 2), respectively. Conclusions. Our tumor stage classification can adequately assess the risk of cancer developing in apparently healthy persons. Cancer 1994; 73:1946-53. Key words: tumor markers, tumor stage, risk assessment, incidence of cancer. From the Asia Medical Center, Saitama, Japan. |
Many researchers have
reported that tumor marker diagnosis may not be useful in the early
detection of cancer because of its low sensitivity (percentage of subjects
diagnosed as having cancer among patients with cancer) and specificity
(percentage of subjects who are not diagnosed as having cancer among normal,
healthy subjects). However, we have proposed a new diagnostic system
consisting of a tumor marker combination assay (using specific tumor
markers, associated tumor markers; and growth-related tumor markers).' With
this new diagnostic system, we have obtained high sensitivity (80-91%) and
high specificity (84-85%).2 In June 1984, we started a program of
substantial tumor marker-based cancer screening using this tumor marker
combination assay, which lasted approximately 2 years. Japan has many screening facilities for cancers of the stomach, lung, uterus, and breast, cancers that are both widespread and generally detectable using conventional morphologic techniques for neoplasms weighing 1 g or more. In contrast to the United States and Europe, where cancer screening is not highly evaluated, it is used extensively in Japan, receiving financial support and promotion from national and local governments as well as the private sector. Conventional stomach and uterine cancer screening techniques, such as radiograph and the Papanicolaou test, obtained a cancer detection rate of only 0.150 (40,200 of 26,733,815 screenees) and 0.092 (25,620 of 27,834,585), respectively.' This incidence of cancer in the general population using conventional morphologic techniques is low. This is not because the techniques are poorly used or administered to the wrong target sample, but because of their limitations, for example, their dependence on the visual characteristics, size, and site of the cancer. The growing neoplasm consists of a cancer cell cluster, a cancer-supporting stroma,4,5 and cancer vessels,6 which produce oncofetal antigen, oncoplacental antigen, and cancer vessel-related substances, respectively. Therefore, we hypothesized that these three substances are important in early cancer detection. Furthermore, because they are identical to tumor-specific tumor markers, tumor-associated tumor markers, and |
This information is provided by Gordon Research Institute. |
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growth-related tumor markers, respectively, we thought that they might play an important role in the tumor marker diagnosis of cancer. According to our model, in cancer development, the growth-related tumor marker appears first, followed by associated tumor markers and specific tumor markers. The presence of these three substances and the order of their appearance are of major significance in cancer screening. Thus, we can classify the tumor stages and use them to make a risk assessment. Our system of staging the tumor development (and the corresponding developmental stage of the actual tumor) is based on the cutoff values of the tumor marker responses, as described below. With our tumor marker combination assay, we can continuously follow the time course of cancer development and discover not only early cancer in a defined organ, but also early cancer at any site. Thus, by identifying a high-risk group, we can decrease the number of patients with cancer by implementing a cancer prevention program, thus achieving true cancer prevention.7-10 In the current paper, we report the detection rate obtained in each developmental stage (from tumor stage I to stage V) and the relationship with risk assessment as well as the question of the reasonableness of our proposed model of natural history of preclinical cancer and its tumor stage classification. Subjects and MethodsSubjects Screened From 1984 to 1986, we performed mass screening for cancer using a combination assay of tumor markers at 15 randomly chosen defined geographic areas in Japan, with a total of 2126 randomly chosen residents (1091 males and 1035 females). Geographic areas, environmental conditions, and the number of screenees are shown in Table 1. The subjects had already been mailed a medical history form requesting such clinical information as past illnesses, present symptoms, and pregnancy. The completed form was handed in on the day of the screening. The subjects were presumably healthy, mostly between the ages of 23 and 80 years, and asymptomatic for cancer (Table 2). Approximately 18 ml of blood was taken from each subject. Serum was separated from the blood by centrifuging and stored at -20°C until the assay. |
Combination Assay of Tumor Markers The serum samples were used for a tumor marker combination assay. The following tumor markers were assayed simultaneously. Carcinoembryonic antigen Carcinoembryonic antigen (CEA) was assayed by enzyme immunoassay using a CEA-EIA Kit (Hoffmann-Roche Co., Ltd., Basel, Switzerland). Heat-stable alkaline phosphatase. Heat-stable alkaline phosphatase (HSAP) was first reported by Fishman et al. as the Regan isoenzyme.4 It has been found in tumor tissue and in the serum of patients with various cancers. HSAP determinations were performed by a modification of the method described by Maslow et al." After 50 ul serum had been heat-treated at 65°C for 7 minutes, it was allowed to react with a fluorescent substrate (naphthol AS-MX phosphate) for 20 minutes at 37°C; it was deproteinized with acetone and the intensity of the fluorescence in the supernatant was measured with a fluoroessence spectrophotometer (Hitachi 650-10, Tokyo, Japan). Ferritin. Ferritin (FT) was assayed by radioimmunoassay using an RIA-gnost Ferritin Kit (Hoechst Behringswerke Aktion Geselshaft, Marlburg, Germany). From clinical experience, we decided to use the ratio of FT to serum iron (FT/Fe) as another tumor marker. Immunosuppressive acidic protein. Immunosuppressive acidic protein (IAP) is characterized by inhibiting both phytohemagglutinin-induced lymphocyte blast formation and mixed lymphocyte reaction in vitro." IAP was determined by means of single radial immunodiffusion using an IAP plate kit (Sanko Jyunyaku Co., Ltd., Tokyo, Japan). Five microliters of sample were applied in each well of an agarose gel plate containing anti-IAP serum, and after incubation for 48 hours at 37°C, the diameter of the precipitation ring was measured. |
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This information is provided by Gordon Research Institute. |
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