CN105242045A

CN105242045A - Use of gastrin-17 as biomarker for atrophic gastritis with increased risk of several related sequels

Info

Publication number: CN105242045A
Application number: CN201410548436.4A
Authority: CN
Inventors: K.西詹恩; O.索瓦尼伊米
Original assignee: Biohit Oy
Current assignee: Biohit Oy
Priority date: 2014-06-13
Filing date: 2014-10-16
Publication date: 2016-01-13
Also published as: CN113514647A; WO2015189480A1; HK1218159A1

Abstract

Gastrin-17 examination relates to the use of gastrin-17 as biomarker for screening symptomless subjects and examining a subject having symptoms in order to find out healthy subjects and subjects with atrophic gastritis due to Helicobacter pylori infection or autoimmune disease. The present invention provides a simple, fast and cost effective method and test for the risk assessment of peptic ulcer disease and diagnosis of atrophic gastritis with related risks.

Description

Gastrin-17 is as the purposes of biomarker of atrophic gastritis of several relevant sequela risks with increase

background information

The present invention relates to the purposes of Gastrin-17 as the biomarker for the manufacture of detection agent, this detection agent is used to the asymptomatic object of examination or checks that those have the object of indigestion symptom, and intention discloses healthy gastric mucosa or has the peptic ulcer of many relevant sequela or the patient's condition of atrophic gastritis risk increase.Optionally, this detection agent also measure helicobacter pylori ( helicobacterpylori) level of antibody.

Helicobacter pylori be in the mucus of the superficial epithelial cells being lodged in contiguous gastric mucosa and space between cells in spirality gramnegative bacterium.This bacterium is obviously shifted to another person from a people by mouth.This bacterium is inflammatory reaction on the impact of gastric mucosa, and it is mediated by various inflammation mediator.If do not eradicated, acute helicobacter pylori infections retains lasting, causes chronic gastritis.Because helicobacter pylori infections and chronic gastritis are closely related, verified this bacteriological infection is one of paathogenic factor in stomach cancer development process.Stage Eliminating H. pylori Infection by Means can prevent the development of atrophic gastritis also thus reduce the risk (US6,696,262) of cancer of the stomach in early days.

50% of all cancer of the stomach (GC) case by advancing to mucosal atrophy, intestinesization raw (IM), dysplasia, developing to " the Correa cascade " of aggressive gland cancer from helicobacter pylori (HP) associated gastritis according to estimates.To prove that, based on the long-term prospective cohort study that the risk of GC in the patient suffering from AG significantly increases, AG is considered to the most potent single independent GC risks and assumptions at present using atrophic gastritis (AG) and IM as the idea of precancerosis condition.Gastrocopy with biopsy is time-honored for diagnosing the method with the premalignant lesion of these stomaches of classification (be re-classified as intraepithelial neoplasia by WHO recently and form (IEN), to evade the interrater agreement unsatisfactory of classifying in the past).Recently, mensuration (GastroPanel) based on ELISA is designed to the serum-concentration measuring following four kinds of stomach specific biomarkers: pepsinogen I (PGI) and II (PGII), Gastrin-17 (G-17) and HPIgG antibody (IgG-HP), make it to become the first for measuring the non-invasive diagnostic instrument of the object (namely those suffer from the object of AG and/or HP) be in GC risk.

As described, atrophic gastritis (AG) is the disease relevant to the risk that cancer of the stomach significantly increases, and is the omen patient's condition of single most important cancer of the stomach (GC) known up to now.On the other hand, helicobacter pylori infection is most important pathogen in gastritis and AG evolution subsequently.AG in stomach hole (antrum) and helicobacter pylori infections can cause GC and peptic ulcer.In body of stomach (corpus), minority AG case is formed by autoimmune mechanism development as everyone knows.The risk of GC is that the 4-5 of the corresponding person of its health is doubly high in the patient suffering serious gastric body mucosa atrophy.This risk suffers from the patient of severe atrophy 18 times high of the object being health at stomach hole, when all there is severe atrophy (namely suffering from serious full lipogastry (panatrophy)) in stomach hole and body of stomach, this risk will be increased to up to 90 times.

Helicobacter pylori infections usually starts from stomach hole and first causes acute shallow HP gastritis.This infection causes HP antibody (HPAB) titre levels in serum to raise, and usually also raises the level of Gastrin-17 as acutely inflamed result.Keep not treating if HP infects, it also gradually affects gastric body mucosa, and result suffers from shallow and chronic HP gastritis.If do not treated, described HP gastritis becomes chronic and causes mucosal atrophy, this atrophy can relate to step by step stomach hole or body of stomach or both.

Except helicobacter pylori infections, atrophic gastritis also develops by the autoimmune mechanism of complexity.Therefore, under the patient suffering from helicobacter pylori infections or autoimmune disease is in the atrophic gastritis risk of increase, atrophic gastritis brings the risk of the cancer of the stomach of increase and cancer of the esophagus and other illnesss several (such as relevant to the shortage of cobalamin, zinc, iron and calcium and the malabsorption of some medicines disease).

The popularity degree of AG and GC increases with the age and raises, and the risk of two kinds of diseases age >45 year object in be the highest.In the elderly, the major part of GC is the intestines hypotype got by the development of AG to GC order.Due to the high risk of cancer in the elderly, at present consistent proposed recommendations is to all dyspeptic the elderlys and those 45(50) year more than people carry out endoscopy.

According to current clinical practice, the conventional program of stomachoscopy comprises gastrocopy, and this inspection is a kind of invasive diagnostic tool allowing most of object feel under the weather.Therefore, need diagnostic tool that is simple, Noninvasive, it is Rapid Implementation and cost-saving detection agent, with detect be in peptic ulcer, atrophic gastritis and the likely increase of consequence risk in object.

Brief summary of the invention

The object of the invention is to some problems at least solving prior art.Specifically, the object of the present invention is to provide method and the detection agent for the asymptomatic object of examination or inspection with the instruction symptom of atrophic gastritis and/or the object of biomarker.

In addition, the object of the present invention is to provide for disclosing high gastric acid output thus reduce as the reliable diagnosis of the risk of peptic ulcer, cancer of the stomach and cancer of the esophagus having in symptom or asymptomatic object.

Or rather, be according to purposes principal character of the present invention, the content stated in the characteristic of claim 1.

Next, the present invention is more thoroughly described by following detailed description of the present invention and embodiment.

detailed description of the present invention and embodiment

The present invention relates to Gastrin-17 as the asymptomatic object of examination with check the Symptomatic object of tool to find healthy object and to suffer from the purposes of biomarker of the object of atrophic gastritis because of helicobacter pylori infections or autoimmune disease.Level by measuring helicobacter pylori antibody discloses the infection of helicobacter pylori.

Biomarker Gastrin-17 (P-G-17) provides the unique opportunity of the atrophic gastritis with simple hematomancy stomach hole.P-G-17 is one of most important peptide hormone of intestines and stomach, plays a role in several functions.G-17 is exclusively secreted by the gastrin cell (G cell) in stomach hole, a part for total gastrin concentration in representative circulation.G-17 part in total gastrin is measured with high specificity by the senior ELISA detection kit of Gastrin-17 (Gastrin-17AdvancedELISATestKit) (Biohit catalog number (Cat.No.) 601035).

When dormancy, the G-cell in stomach hole only secretes a small amount of G-17 hormone.After physiologic proteic stimulates (" steak stimulations " or albumen stimulate), or when minimizing, low or when not having is secreted in acid in stomach, reach maximum secretion.Due to stomach hole atrophy (that is, anadenia), the quantity of G-cell reduces, thus basis and the secretion of gastrin after the meal all reduce.

P-G-17ELISA method specificity is for " amidation " G-17 molecule.G-17 peptide is the most important member of gastrin/pancreozymin family, and it regulates upper gastrointestinal physiological function.This peptide is the To Gastrin Peptide Radioimmunoassay that biologically active is the strongest, with the effect gastric acid secretion of 6 times of the gastrin G-34 of biologically active the last the second high.G-17 specific detection allows not to be had background noise and with under G-34 peptide or the same cross reaction situation being derived from other gastrin segments in the source being different from G-cell, is assessing quantity and the function of stomach hole G-cell.The IHC that G-17 monoclonal antibody is also suitable for the paraffin-embedded sample that formalin is fixed analyzes.As a reference, the gastrin determination method used in the laboratory of most of hospital at present measures the level of total gastrin (i.e. all biologically active To Gastrin Peptide Radioimmunoassays).

Road as known, helicobacter pylori infections is the most important reason causing chronic gastritis.Another well-known reason causing gastritis and serious AG (atrophic gastritis) is autoimmune mechanism, and it also can be activated by helicobacter pylori infections.The ELISA of helicobacter pylori detects usual plasma sample and implements.This detection is based on the Heliobacter pylori antigen using the purifying be adsorbed on microplate and the enzyme immunoassay technique carried out with the detection antibody that horseradish peroxidase (HRP) marks.

gastrin-17 checks and associated biomarkers

Based on the comparative study undertaken by gastrocopy and biopsy specimen inspection, confirmed this innovation biomarker detection agent Gastrin-17 (G-17) and if desired helicobacter pylori IgA and IgG antibody complimentary to one another to form diagnostic bank.Helicobacter pylori IgA and IgG antibody are the marks of helicobacter pylori infections, and the level of the G-17 usually recorded in fasting blood sample is the mark of the function and structure of antrum.The GastroSoft computer program of customization is used for the explanation of Gastrin-17 check result.For obtaining whole benefit, importantly will note from same blood (blood plasma) sample, measuring Gastrin-17 biomarker as group (panel), optional use GastroSoft is to help explanation results.

Gastrin-17 inspection is intended for safety, morals and diagnosing and examination indigestion, helicobacter pylori infections and atrophic gastritis and relevant risk (10-21) cost-savingly.These risks comprise the shortage of stomach and cancer of the esophagus, peptic ulcer and cobalamin, iron, zinc and calcium.Gastrin-17 also contributes to the development assessing gastroesophageal reflux disease (GERD) and complication thereof, and such as erosive esophagitis and Barrett (Barrett) esophagus, it can cause cancer of the esophagus.Gastrin-17 is suitable for diagnosis atrophic gastritis and is suitable for indicating the reason causing atrophic gastritis.If not suffered from by the patient being diagnosed as atrophic gastritis based on G-17 level and never suffer from helicobacter pylori infections (helicobacter pylori IgA and IgG antibody detect and medical history), atrophic gastritis is probably caused by autoimmune disease.

The assessment of the function and structure of the antrum undertaken by Gastrin-17 inspection is of crucial importance, and reason is that atrophic gastritis starts from distal stomach (stomach hole and Qi Jiao) as a rule, and it can extend upwardly to body of stomach from here.The antibody of low G-17 and helicobacter pylori IgA and IgG is the biomarker of stomach hole atrophic gastritis.The patient with helicobacter pylori infections and low G-17 suffers from the antral gastritis of atrophic and/or is characterized as the high risk so-called mastery antral gastritis (antralpredominantgastritis) of peracid secretory volume and peptic ulcer.Due to the risk of the increase of premalignant lesion or early-stage cancer in stomach hole, these patients should carry out gastrocopy and biopsy sample detects.These patients also may be in the increase risk that GERD (gastroesophageal reflux disease) and complication (Barrett esophagus and cancer of the esophagus) thereof occur.

Term " biomarker " means the measurable change occurred in the Biochemical processes of biosome, compound or organelle in this article.Cause the reason of such change may be the such as such as disease such as helicobacter pylori infections or atrophic gastritis.

According to a preferred embodiment of the present invention, using Gastrin-17 as biomarker for the manufacture of be used for the asymptomatic object of examination (that is, people) or check have instruction helicobacter pylori infections and/or the symptom of atrophic gastritis and/or the object of biomarker method in detection agent.The method preferably includes the concentration (basis and/or stimulate) of quantitative measurment Gastrin-17 from biological specimen (be preferably and gather from the blood of described object, blood plasma or serum sample), and by the value of acquisition compared with indicating the predetermined reference scope of healthy gastric mucosa.From described biological specimen, the level of quantitative measurment helicobacter pylori antibody (HPAB) also may be useful.In addition, the method preferably includes quantitative measurment and is selected from option a)-e) concentration and level:

A) Gastrin-17 B (basis) is or/and Gastrin-17 S (stimulation);

B) Gastrin-17 B and helicobacter pylori IgG;

C) Gastrin-17 B, helicobacter pylori IgG and IgA;

D) Gastrin-17 B, Gastrin-17 S and helicobacter pylori IgG;

E) Gastrin-17 B, Gastrin-17 S, helicobacter pylori IgG and IgA.

According to another embodiment of the present invention, described Gastrin-17 and helicobacter pylori antibody are used as biomarker and are used for the risk disclosing high gastric acid output and consequential peptic ulcer.In addition, Gastrin-17 and helicobacter pylori antibody are preferred for reducing peptic ulcer and/or cancer of the stomach and/or GERD(gastroesophageal reflux disease having in symptom or asymptomatic object) and complication: the risk of Barrett esophagus and cancer of the esophagus.

Based on result of the present invention, if in described sample Gastrin-17 concentration close to term of reference lower limit or lower than term of reference or close to the upper limit of term of reference or higher than term of reference, this inspection just indicates atrophic gastritis.

Next, the diagnostic classification based on the result checked from Gastrin-17 is more thoroughly described.

the diagnostic classification checked based on Gastrin-17 and result and representative value thereof

Not there is the instruction symptom of autoimmune disease and/or the object of biomarker, namely

Healthy gastric mucosa:

● HP antibody horizontal (HPAB) negative (<30EIU)

● Gastrin-17 B (fasting): 1-7pmol/l

● Gastrin-17 S (stimulation): 3-30pmol/l

Non-atrophic (HP) antral gastritis:

● the HPAB level (>30EIU) of increase

● Gastrin-17 B normal (1-7pmol/l) or increase (because infecting)

Atrophic antral gastritis:

● the HPAB level (>30EIU) of increase

● Gastrin-17 B low (<1pmol/l)

● Gastrin-17 S is low, does not increase above reference value (3pmol/l)

Atrophic body of stomach inflammation (atrophiccorpusgastritis):

● increase or normal HPAB level (<30EIU, HP can lack)

● Gastrin-17 B increases (>7pmol/l) (feedback from the body of stomach of anacidity)

● Gastrin-17 S is nonessential

The general gastritis of atrophic (PANGASTRITIS) (stomach hole and body of stomach):

● increase or normal HPAB level (<30EIU, HP can lack)

● Gastrin-17 B low (<1pmol/l)

● Gastrin-17 S does not increase above reference value (3pmol/l)

Therefore based on more than, Gastrin-17 detects the state only can not distinguished between atrophic antral gastritis and the general gastritis of atrophic, because based on the stomach hole of atrophy in both, result is similar.From prior art known GastroPanel, both of these case is distinguished, because it directly measures the activity of body of stomach with biomarker PGI and PGII.But Gastrin-17 directly measures the activity of stomach hole and the activity (when there is not biomarker PGI and PGII) of indirect inspection body of stomach, thus provides more cheap detection and more simply analyzes.

Therefore, according to an embodiment, the activity of antrum is directly measured according to Gastrin-17 inspection of the present invention.In addition, this inspection provides the collateral information of the activity about body of stomach based on the physiology positive feedback between stomach hole and body of stomach and negative feedback mechanism.The HPAB value (more than 30EIU) increased indicates helicobacter pylori infections usually.

gastrin-17 check result and explanation thereof

The GastroSoft program that Gastrin-17 check result customizes made an explanation, testing result is directly sorted out to one of previously mentioned classification by this program.In addition, final diagnosis needs the output from healthcare givers, exceedes a kind of clinical diagnosis option because exist for the partial results obtained by Gastrin-17 inspection.

1) HPAB level is normal and G-17B is normal:

● the gastric mucosa of 1.1. health

2) the HPAB level increased and G-17B that is normal or that increase:

● in 2.1. stomach hole, shallow HP-infects

● in 2.2. body of stomach, shallow HP-infects

3) G-17B of that increase or normal HPAB level and increase:

● 3.1. atrophic body of stomach inflammation (anacidity stomach, HP+ or HP-)

● 3.2.PPI-medicinal treatment (anacidity/low sour stomach) (HP-)

4) HPAB increased and low G-17B:

● 4.1. is peracid secretion (negative feedback) in body of stomach

● 4.2. atrophic antral gastritis (G Cells Depletion)

● the general gastritis of 4.3. atrophic (all atrophys of stomach hole and body of stomach)

5) the HPAB level increased and low G-17S secrete:

● 5.1. atrophic antral gastritis (G Cells Depletion)

● the general gastritis of 5.2. atrophic (all atrophys of stomach hole and body of stomach)

diagnosis follow-up

Because in some situation (above option 2.1-5.2), Gastrin-17 check result can relate to more than a kind of actual clinical situation, need to carry out a small amount of simple follow-up to end at last diagnosis:

Option 2:

● this difference is not remarkable clinically, and thus HP-eradication therapy is all sufficient measure in both cases.

Option 3:

● from PMI information, inquire PPI medicinal treatment, which differentiation situation 3.1 and 3.2 should be illustrated if necessary.

● HP eradication therapy (success) eradicate infection, G-17 becomes normally, thus confirms situation 2.1.

Option 4:

● low G-17B confirms by carrying out G-17S, takes this low value and is defined as situation 4.2.

● alternatively, the PPI medicinal treatment in test 1-2 week, if G-17 recovers normal, gets rid of situation 4.3 and 4.3, takes this situation that turns out to be 4.1.

Option 5:

● it is impossible for only carrying out differentiation with Gastrin-17 inspection.

● carry out GastroPanel-detection, confirm or get rid of situation 5.2.

● carry out gastrocopy, confirm diagnosis with biopsy.

the atrophy of stomach hole and peracid secretion.

Gastrin-17 inspection implements (such as in 22) to fasting plasma sample usually.If the patient suffering from helicobacter pylori infections and low G-17 does not want to carry out invasive gastrocopy, the concentration additional fasting Gastrin-17 inspection by measuring the G-17 that albumen stimulates in blood plasma confirms or gets rid of the atrophic gastritis of stomach hole.When the atrophy of stomach hole, the fasting levels of G-17 for want of G cell and low, and albumen stimulates the level that can not improve G-17.Hydrochloric acid in gastric juice and then suppress the secretion of G-17, and when only high Acidity in the stomach, albumen stimulates the blood plasma level (in stomach hole, G cell colony is normal) significantly improving G-17.Therefore, by having the patient of atrophic gastritis and its G-17 fasting concentrations in stomach hole, low to secrete that those patients caused distinguish by peracid be completely possible.

Under normal conditions, if stomach hole does not have atrophy, the level of the G-17 in blood is increased to exceed 7.0pmol/l by albumen stimulation.If the G-17 concentration ratio 3.0pmol/l that albumen stimulates is few, and this patient suffers from helicobacter pylori infections, then probably this patient suffers from the atrophic gastritis of antrum.Low G-17, the atrophy of stomach hole and peracid secretion between relation made an explanation by the physiological feedback mechanism between known stomach hole and body of stomach.Do not suffer from helicobacter pylori infections and G-17 fasting value stimulate lower than 2.0pmol/l and albumen after the patient that improves of G-17 level, may be in the risk of severe complication (erosive esophagitis and Barrett esophagus) of gastroesophageal reflux disease (GERD).If the fasting levels of G-17 is 1.0pmol/l or lower, this risk obviously more likely.

Activity and the preferred structure of antrum are directly measured in Gastrin-17 inspection, and provide the collateral information about body of stomach activity (and structure).This is owing to the physiology positive feedback between body of stomach and stomach hole and negative feedback mechanism.Secretion from the activity (pepsinogen I (PGI) and pepsinogen I I(PGII) of prior art (GastroPanel) known body of stomach) be directly related with the quantity of the specific cells of mucous membrane.Therefore, the activity of body of stomach also illustrates the structure of body of stomach, the same in thus detecting with GastroPanel.Difference between Gastrin-17 inspection and GastroPanel detect is that the latter directly measures helicobacter pylori antibody (HPAB), Gastrin-17, PGI, PGII and PGI/PGII ratio, and Gastrin-17 level and optional HPAB level are only directly measured in Gastrin-17 inspection, therefore based on the level of the biomarker previously described with this instructions detected by researchist, provide and more simply analyze.

Therefore, the early diagnosis of the detection of G-17 and stomach hole atrophic gastritis subsequently provides the possibility of the patient found out in the remarkable risk being in cancer of the stomach in stomach hole, provide the instrument for describing the object be in peptic ulcer particular risk, and the patient making it possible to describe to be in the most excessive risk of cancer of the stomach, namely those suffer from expansion and the patient of serious atrophic gastritis in stomach hole and body of stomach.

the risk of cancer of the stomach and peptic ulcer

The risk that the people in stomach hole with medium or serious atrophic gastritis (low G-17 and helicobacter pylori IgA & IgG antibody) gets a cancer of the stomach is 18 times of the people of health.The risk " only " that the people in body of stomach with medium or serious atrophic gastritis gets a cancer of the stomach is 5 times of the people of health.If all suffer from medium or serious atrophic gastritis in stomach hole and body of stomach, the risk of cancer is 90 times high (8).Due to the risk of cancer of the stomach, this information especially helps to recognize that detecting G-17 is how extremely important (safety, morals and cost-saving; According to this area law ( legeartis)).

G-17 is also the biomarker of peptic ulcer risk.Bleeding peptic ulcer is the severe complication of peptic ulcer, increasing because of the use of NSAID medicinal treatment, seizes the life of 200-300 people every year in Finland's (population 5,200,000).By contrast, annual approximately 400-600 people dies from the cancer of the stomach in late period.Being checked by Gastrin-17 correctly diagnoses the people be in peptic ulcer risk to exempt from unnecessary complication by making people, even exempts from death.In addition, can conceivablely be check that the people of examination more than 45 years old will make 250-300 people exempt from the unnecessary death (patient can be found curing the stage) (9) caused by cancer of the stomach every year at Finland's Gastrin-17.

PPI gastrin-17 inspection before medicinal treatment

Gastrin-17 inspection can be applicable to and is applicable to use before PPI medicinal treatment, to determine that patient does not suffer from atrophic gastritis and hypochlorhydria or even gastric anacidity stomach.In addition, PPI treatment can be alleviated, and thus covers the symptom of the such as serious disease such as cancer of the stomach and bleeding peptic ulcer, thus can delay appropriate Diagnosis and Treat.

the hypochlorhydria caused by corpus atrophy and PPI

The hypochlorhydria caused by corpus atrophy and PPI also allow people have an aptitude to from oral cavity or lower intestinal tract microorganism to stomach determine grow.In the consumption process of carbohydrates forming the most balanced meals part, the oral bacteria surely grown causes the generation of carcinogenic acetaldehyde by fermenting under one's belt.The risk that the hypochlorhydria of stomach increases strongly with cancer of the stomach is associated (24-25).The minimizing for the treatment of the intestinal absorption of the calcium caused by atrophic gastritis and long-term PPI easily causes the risk (26) of such as osteoporosis and hip fracture.In addition, just know that the such as hypochlorhydria such as atrophic gastritis and gastric resection state is the reason (27) producing hypoferric anemia for a long time.

the shortage of cobalamin

The atrophic gastritis do not diagnosed out usually causes the shortage of cobalamin, and this shortage seems to affect the elderly population (16) up to 10%.The shortage of cobalamin is considered to relevant to development that is dull-witted, depressed and peripheral neurophaty.This shortage raises the concentration of homocysteine of the independent risk factor being counted as atherosclerotic, heart attack and apoplexy in all tissues and cell.If detect in early days and treat, shortage and its origin cause of formation of cobalamin are reversible, but unfortunately, this is few situation.

sum up

When Gastrin-17 inspection instruction gastric mucosa is healthy, indigestion symptom is usually caused by functional dyspepsia FD or the another kind of disease that do not relate to gastric mucosa.Gastrin-17 inspection can be used for really needing gastroscopic patient not distinguish in the urgent need to gastroscopic patient with those.Make limited endoscope resources conservation in this way and rationalize to be used for prior object and to become possibility.The indigestion symptom of similar 50% may be colon origin, especially in elderly population.

In addition, consider that the patient suffering from atrophic gastritis and relevant risk (shortage of cancer of the stomach, peptic ulcer and cobalamin, iron, zinc and calcium) does not usually have symptom, Gastrin-17 examination was carried out to the entire population of more than 45 years old and will contribute to finding the gastroscopic individuality of needs.Although can implement this, and have little or unconspicuous change relative to the present situation on the gastroscopic sum of needs, it can produce significant improvement in test-and-treat serious disease aspect in early days.Except diagnosing helicobacter pylori and atrophic gastritis, the result of Gastrin-17 inspection also can be used for the risk of suitability that assess patient treats PPI and demand and GERD complication.

helicobacter pylori is replaced with Gastrin-17 inspection ¹³ c-urea breathing detection and Stool antigen test

The fact stated above highlights why indigestion and helicobacter pylori patient and should not pass through ¹³c-urea breathing detection or Stool antigen test detect, even if they are included in current " test-and-treat " strategy.They only detect helicobacter pylori infections but do not detect other things, may even in the correct diagnosis detected ongoing helicobacter pylori unreliable (1-3).If patient suffers from atrophic gastritis, MALT lymthoma or bleeding peptic ulcer disease, if or patient is current is accepting microbiotic or PPI, then ¹³c-urea breathing detection and Stool antigen test provide the false negative result (28-34) of 40 – 50%.These are situations of wherein helicobacter pylori test-and-treat particular importance reliably.Helicobacter pylori IgA & IgG antibody detects the false negative result that combination does not have these types.

In addition, there is another reason (37,38) helicobacter pylori IgA & IgG antibody being detected and be used for helicobacter pylori and detect: " nearly all infected individuality (>90%) all shows helicobacter pylori specific IgG antibodies.The great majority (about 70%) of these individualities also show IgA antibody.The infected individuals of about 7% presents the positive to IgA antibody but presents feminine gender to IgG antibody; The reason of this exception response is still unclear.”

By reference to research and the scientific literature of the people such as professor Pasechnikov (14), draw to draw a conclusion: " reach a conclusion to the analysis let us of our result of study and data in literature: the serious medical of " test-and-treat " strategy and the question of morality can simply and replace it by checking with GastroPanel economically ¹³c-urea breathing detection or Stool antigen test and revise.This is equally applicable to Gastrin-17 inspection.The people such as Talley (2004) point out that, in a lot of country such as such as Sweden and the U.S. etc., independent " test-and-treat " strategy is not considered to enough (37).The helicobacter pylori of " test-and-treat " strategy detects does not find atrophic gastritis and the such as relevant risk such as cancer of the stomach and premalignant lesion, and it should be confirmed and successful treatment by gastrocopy and biopsy specimen inspection.Therefore, Gastrin-17 & gastrocopy and biopsy specimen inspection disclose the patient with premalignant lesion and early carcinoma of stomach, thus make people avoid the unnecessary death suffering to be caused by cancer of the stomach.”(1-3)。

gastrin-17 inspection helps to avoid treatment accident and consequence thereof

Use ¹³c-urea breathing detection or Stool antigen test delay correct Diagnosis and Treat, the unnecessary death can cause treatment accident, even being caused by cancer of the stomach and the bleeding peptic ulcer of such as error diagnosis.In addition, the inaccurate detection even misleading people is used to cause the unnecessary cost of health care, social security, insurance company, employer and patient self.Now, when GastroPanel and Gastrin-17 inspection can utilize, to suffer from indigestion, helicobacter pylori infections and atrophic gastritis and relevant risk thereof (shortage of cancer of the stomach, peptic ulcer and cobalamin, iron, zinc and calcium) patient Diagnosis and Treat in abandon old detection ( ¹³c-urea breathing detection or Stool antigen test) be rational and morals.

Leader of opinion, laboratory and doctor have the authority that do not hold query and responsibility goes to recommend, propose and use the available inspection and the treatment that have feasibility most.Now, gastric mucosa correct and comprehensive, safe and in the inspection of morals, only have 3 kinds of available selections.They are: the 1) histological examination 2 of gastrocopy and biopsy sample) GastroPanel inspection and 3) Gastrin-17 inspection.

In primary care and human health screening particularly when endoscope inadequate resource, especially preferably Gastrin-17 inspection.When Gastrin-17 inspection is compared with gastrocopy, accurate diagnosis can not be made according to a small amount of biopsy specimen.In the patient suffering from atrophic gastritis, although ¹³c-urea breathing detection and Histological results are negative, and positive serology (helicobacter pylori IgA & IgG antibody) result can indicate ongoing helicobacter pylori infections (31-34).In addition, the histodiagnosis of two virologists may difference.Histological quality depends critically upon experience and the ability of gastroenterologist and virologist.

Because the biomarker measured in blood provides the objective information of the function and structure about gastric mucosa had nothing to do with the people detecting them, Gastrin-17 inspection and these problems have nothing to do.When these biomarkers exist alarm change, after Gastrin-17 inspection, then careful gastrocopy must be carried out.In this case, the information provided by Gastrin-17 is very useful.Gastrin-17 inspection prevent unnecessary gastrocopy and help by rare endoscope resource suitably, in particular target be surely used for colorectal cancer screening.Dyspeptic, its gastric mucosa of 50 years old or higher, through finding out healthy patient, should seek help from colonoscopy because the stomachache of similar half and stomach trouble to can be colon relevant.

In medicine, obviously good diagnosis and appropriate treatment are gone forward hand in hand.This viewpoint is constructed in product development by supporting the joint development that new drug and diagnosis are developed by business circles and food and FAD (FDA) regulators further.The combination of the PPI treatment of this newly developed and Gastrin-17 diagnosis with GERD and the microbiotic with helicobacter pylori infections and PPI treatment is by promotion safety, morals and cost-saving, evidential preventative medicine.

Management organization should require to carry out Gastrin-17 inspection before any PPI medical expense of reimbursement GERD.In addition, to be checked by Gastrin-17 or the reliable diagnosis of helicobacter pylori infections that the gastrocopy professionally implemented and biopsy specimen inspection (gastrocopy) are carried out and relevant risk should be the basis of reimbursement Eradication Therapy of Helicobacter pylori expense.

This for developing safety, morals and the expense of health care is reduced in essence Shangdi by the guiding of cost-saving evidential preventative medicine and contribution, and prevent disease, promote healthy, even avoid the unnecessary death such as caused by cancer of the stomach and bleeding peptic ulcer.

It has been the unique method being applied to examination safely and diagnosing dyspepsia, atrophic gastritis and cancer of the stomach (the second the most general reason of global cancer related mortality) that gastroscope detects.After the risk assessing atrophic gastritis and cancer of the stomach, researchist has drawn such conclusion: Gastrin-17 and helicobacter pylori antibody can be effectively applied to examination indigestion, atrophic gastritis and cancer of the stomach (9,11-14,19-21,39,40).

At present, the examination of atrophic gastritis and relevant risk (shortage of cancer of the stomach, peptic ulcer, cobalamin, iron, zinc and calcium) is considered to 45 years old and the nursing standard of more old people.Its carelessness may be the common cause of the lawsuit caused by treatment accident, and when the carelessness of the colorectal cancer screening of the people for 50 years old or higher age, it has been considered to treatment accident (41).

list of references and Relevant Publications

(1)https://nobelprize.org/medicine/laureates/2005/press.html

(2)https://www.yourhealthbase.com/database/rulcer_drugs.htm

(3)https://www.gastropanel.net

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(101) people such as MauryCPJ. the atrophic gastritis in Sjogren syndrome.Morphology, biological chemistry and immunology find (AtrophicGastritisinsj gren'ssyndrome.Morphologic, biochemical, andimmunologicfindings) .ArthritisandRheumatism2005; 28 (4): 388-394).

(102) people such as IshikawaN. the helicobacter pylori infections in rheumatoid arthritis: the effect of medicine pop and damage with gastroduodenal associate (Helicobacterpyloriinfectioninrheumatoidarthritis:effecto fdrugsonprevalenceandcorrelationwithgastroduodenallesion s) .Rheumatology2002; 41:72-77.

(103) people such as SalonenEM. the anti-telomere antibody in systemic lupus erythematosus (SLE): comparison (Anti-telomereantibodiesinsystemiclupuserythematosus (SLE): the acomparisonwithfiveantinuclearantibodyassaysin430patient swithSLEandotherrheumaticdiseases) .AnnRheumDisease2004 carried out with 5 kinds of antinuclear antibody assays in 430 patients suffering from SLE and other rheumatoid diseases; 63 (19:1250-1254.

(104) people such as WallaceDJ. the anti-telomere antibody in systemic lupus erythematosus: for new ELISA test (Anti-telomereantibodiesinsystemiclupuserythematosus:anew ELISAtestforanti-DNAwithpotentialpathogenicimplications) with the potential pathogenic anti-DNA involved.

Claims

1. Gastrin-17 as biomarker for the manufacture of have for the asymptomatic object of examination or inspection instruction helicobacter pylori infections and/or the biomarker of atrophic gastritis and/or the object of symptom method in detection agent in purposes, it is characterized in that the method comprises the concentration measuring Gastrin-17 from the biological specimen taking from described object quantitatively, and by income value compared with the term of reference of the gastric mucosa of predetermined instruction health.

2., according to the purposes of claim 1, it is characterized in that described method comprises measuring quantitatively and be selected from option a)-e) the concentration of biomarker and level:

A) Gastrin-17 B(basis) or Gastrin-17 S(to stimulate),

B) Gastrin-17 B and helicobacter pylori IgG,

C) Gastrin-17 B, helicobacter pylori IgG and IgA,

D) Gastrin-17 B, Gastrin-17 S and helicobacter pylori IgG;

E) Gastrin-17 B, Gastrin-17 S, helicobacter pylori IgG and IgA.

3., according to the purposes of claim 1 or 2, it is characterized in that described biological specimen is blood, serum or plasma sample.

4., according to the purposes that claim 1-3 is one of any, it is characterized in that described detection agent directly measures the activity of antrum.

5., according to the purposes of claim 4, it is characterized in that described detection agent provides the collateral information about body of stomach activity based on the physiology positive feedback between stomach hole and body of stomach and negative feedback mechanism.

6. according to the purposes of claim 1 or 2, it is characterized in that the described term of reference indicating healthy gastric mucosa is 3-30pmol/l for Gastrin-17 S, being 1-7pmol/l for Gastrin-17 B, is lower than 30EIU for HPAB (helicobacter pylori antibody) level.

7., according to the purposes of claim 6, it is characterized in that in the sample more than the HPAB level instruction helicobacter pylori infections of 30EIU.

8. according to the purposes of claim 6, it is characterized in that in the sample close to term of reference lower limit or lower than term of reference or close to term of reference the upper limit or exceed the Gastrin-17 value instruction atrophic gastritis of term of reference.

9. according to the purposes of claim 6, it is characterized in that if Gastrin-17 B value be 1-7pmol/l and HPAB value more than 30EIU, described value indicates non-atrophic gastritis.

10. according to the purposes of claim 6, it is characterized in that if Gastrin-17 B value is lower than 1pmol/l, Gastrin-17 S value lower than 3pmol/l and HPAB value lower than 30EIU(when HP lacks) or more than 30EIU, then described value instruction atrophic antral gastritis or the general gastritis of atrophic.

11. according to the purposes of claims 6, it is characterized in that if gastrin-17B value higher than 7pmol/l and HPAB value lower than 30EIU(when HP lacks) or more than 30EIU, then described value indicates atrophic body of stomach inflammation.

12. gastrins-17 and optional helicobacter pylori antibody are as the purposes of the biomarker of the risk for disclosing high gastric acid output and consequential peptic ulcer.

13. gastrins-17 and optional helicobacter pylori antibody are as asymptomatic or have in symptom object the purposes of biomarker of the risk reducing peptic ulcer.

14. gastrins-17 and optional helicobacter pylori antibody are as asymptomatic or have in symptom object the purposes of biomarker of the risk reducing cancer of the stomach.

15. gastrins-17 and optional helicobacter pylori antibody are as asymptomatic or have in symptom object and reduce gastroesophageal reflux disease and complication thereof: the purposes of the biomarker of the risk of Barrett esophagus and cancer of the esophagus.