GastroPanel® (Panel of Biomarkers) as the First-Line Diagnostic Test for

Dyspeptic Symptoms and in Screening for the Risk Groups of Gastric Cancer

Prof. Osmo Suovaniemi, MD, PhD Chairman of the Board

Biohit Oyj, Finland

GastroPanel® – a test for stomach health

Corpus

Antrum

Pepsinogen I & II; Pepsinogen I/II ratio are biomarkers of gastric corpus

Amidated gastrin-17 is biomarker of antrum (G cells), together with Pepsinogen II

H. pylori IgG antibodies are markers of HP-associated gastritis (antrum & corpus)

Pylorus

Esophagus

GastroPanel® test – a panel of 4 biomarkers

The First-Line Diagnostic Test for Patients with Dyspeptic Complaints

For Screening of the Subjects at Increased Risk for Gastric Cancer

GastroPanel® test – indications for use

GastroPanel® – dyspepsia (Stomach pain or discomfort)

Dyspepsia is not a specific symptom Affects some 20-40% of the population Correct diagnosis is not possible by symptoms alone H.pylori infection and atrophic gastritis (AG), the most important clinical conditions behind dyspepsia Gastroscopy is the usual first-line diagnostic tool GastroPanel blood test will help sorting out the patients who truly need endoscopy (Gastroscopy ) GastroPanel saves unnecessary gastroscopies and costs.

GastroPanel® – risk factors of gastric cancer

Helicobacter pylori infection:

Relative risk=

3.0–13.3

Atrophic gastritis:

Relative risk =

up to 90

Ref: smoking and lung cancer: OR=12 HPV16 and cervical cancer: OR>400

PGI, PGI/II ratio

“Correa’s cascade”

Normal mucosa

Chronic gastritis

Atrophic gastritis

Intestinal metaplasia Dysplasia

Gastric Adenocarcinoma

Intestinal type

Gastric Adenocarcinoma

Diffuse type

corpus

antrum

G17

Correa P. Cancer Res 1992;52:6735-6740.

?

HP and AG - two diseases, one diagnostic test

GastroPanel: WHY?

1 0.5 0.1 0.1 0.1

10 10 2 1 0.5

22 22 3 2 1

26 26 3 2 1

26 26 3 2 1

0 1 2 3 4

0

2

3

4

1 1 1 2 5

1 2 2 2 5

2 2 2 3 5

2 2 4 5 10

18 18 36 36 90

0 1 2 3 4

0

1

2

3

4

1

an

tru

m

corpus corpus

RISK OF ULCER: RISK OF GC:

0=normal; 1=non-atrophic gastritis; 2=mild AG, 3=moderate AG; 4=severe AG

Sipponen et al. Int J Cancer 1985; Scand J Gastroenterol 1989

Phenotype of gastritis - risk for GC is different

HP and AG- two diseases, one diagnostic test

GastroPanel: HOW?

Atrophic gastritis in the corpus

Atrophic

Corpus

Gastritis:

HCl ↓

PGI ↓

PG II↓ Antrum

G-17

Protein

Blood

circulation

G-17

Normal

Corpus:

PGI and PGII

normal or high

Atrophic

Antrum

Gastritis:

G-17 ↓

Protein

Atrophic gastritis in the antrum

Blood

circulation

G-17↓

GastroPanel® – results reported by GastroSoft®

GastroPanel® – the diagnostic algorythm *The GastroPanel report contains a more detailed interpretation. Source: Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Agreus L, Kuipers E, Kupcinskas L, Malfertheiner P, DI Mario F, Leja M, Mahachai V, Yaron N, Van Oijen M, Peres Peres Q, Rugge M, Ronkainen J, Salaspuro M, Sipponen P, Sugano K, Sung J. Scand J Gastroenterol 2012;47:136-47. Available also on www.biohithealthcare.com/research

GastroPanel® – stomach is healthy

H.pylori G-17 PGI PGII PGI/PGII Antrum Corpus

EIU pmol/l µg/l µg/l

30 1-7 30 - 160 3 – 15 3 - 20

2 8 75 10.1 N N

All GastroPanel biomarkers are normal !!

Risk of cancer or peptic ulcer is nil – irrespective of age.

Gastroscopy does not give any significant information

Colonoscopy or other clinical examinations are more useful and cost-effective.

GastroPanel® – severe atrophy in the corpus

H.pylori G-17 PGI PGII PGI/PGII Antrum Corpus

EIU pmol/l µg/l µg/l 30 1-7 30 - 160 3 – 15 3 - 20

150 363 5 3.5 1.4 N N

PGI is low indicating that corpus is severely atrophic. The PGI/PGII ratio (1.4) is low (below 3,0)

Amidated G-17 is high indicating that antrum is normal and that acid secretion is low

H.pylori antibodies are elevated. Atrophic gastritis is due to H.pylori infection.

Gastroscopy is mandatory for cancer risk. Risk of malabsorption of vitamin B12, calcium (risk of osteoporosis), iron, magnesium and zinc. Absorption of pharmaceuticals unpredictable. Stomach is achlorhydric (no acid) and colonized with bacteria and fungi. Carcinogenic acetaldehyde is produced in stomach.

See Appendix 1

GastroPanel® – three categories of risk

“Healthy”, normal stomach mucosa:

No risk of gastric cancer or ulcer

Non-atrophic H.pylori (Hp+) gastritis: High ulcer risk, low cancer risk.

Atrophic gastritis (Hp+ or Hp-):

High cancer risk, low ulcer risk. High risk of mal- absorption of vitamin B12, calcium, iron, magnesium and

zinc. Stomach is acid-free and colonized with bacteria and fungi. Carcinogenic acetaldehyde appears in stomach.

GastroPanel® – three approaches of management

“Healthy”, normal stomach mucosa:

No need for prompt gastroscopy(save costs)

Non-atrophic H.pylori (Hp+) gastritis: Patient and physician may decide of further

treatment and examinations. Consider eradication of H.pylori!

Atrophic gastritis (Hp+ or Hp-):

Gastroscopy is mandatory. Eradication of H.pylori is necessary.

GastroPanel® – a rational for using

H.pylori-infection is causally related to AG, and treatment is indicated (Maastricht IV recommendations) GastroPanel provides an easy, cheap and comprehensive non-endoscopic diagnostic option GastroPanel provides more information than is possible to obtain by H.pylori-infection testing alone GastroPanel enables objective ranking of patients for endoscopy

Patient with dyspeptic complaints

GastroPanel® – the cost-effective diagnostic tool

Benefits of GastroPanel are two-fold:

Detects the subjects with healthy stomach

Detects the patients at increased risk for cancer/ulcer

GastroPanel®

Healthy stomach

Gastroscopy

Acetium® Capsule

TO THOSE WITH ACID

FREE STOMACH

• Atrophic gastritis

• Use of PPI-drugs

• Operated stomach

• Chronic Helicobacter

pylori infection

• May cure atrophic

gastritis (further studies are

needed)

No other similar

preparation

available

Acetium® Lozenge

• To smokers

–Eliminates >90% of carcinogenic

acetaldehyde from saliva

• Harm reduction (L-cysteine and Xylitol

eliminate carcinogenic acetaldehyde in saliva)

• May help stop tobacco

smoking (further studies are needed)

• No other similar preparation

available

Study Protocols Provided by BIOHIT Oyj

Clinical Trial with the Biohit HealthCare GastroPanel® Assay for Early Detection of Patients at Risk for Gastric Cancer.

(GastroPanel Clinical Study)

Biohit HealthCare GastroPanel® Assay In Screening of Patients at Risk for Gastric Cancer. (GastroPanel Screening Study)

A new-generation immunochemical fecal occult blood test [ColonView Hb and Hb/Hp Test] compared to quaiac-based test

(Hemoccult®SENSA®) in detection of proximal and distal colorectal neoplasia among colonoscopy referral patients.

(ColonView Clinical Study)

A new-generation immunochemical fecal occult blood test [ColonView Hb and Hb/Hp Test (30)] compared to quaiac-based test

(Hemoccult®SENSA®) in colorectal cancer (CRC) screening. (ColonView Screening Study)

Performance of the CELIAC Quick Test® in Diagnosis of Celiac Disease in a Biopsy-Controlled Clinical Trial.

(Celiac Quit Test Clinical Study)

The Efficacy of Acetium Lozenges in Intervention for Smoking Cessation. A double-blind, placebo-controlled trial.

(Acetium in Smoking Quit Study)

Efficacy of L-cysteine in Prevention of Headache Attacks in Migraine Patients. Randomized Intervention Trial with a Medical

Device (Acetium™ Capsules). (Acetium in Migraine Prevention Study)

The Efficacy of L-cysteine in Prevention of Cluster Headache. Randomized Intervention Trial with a Medical Device (Acetium™

Capsules). (Acetium in Prevention of Cluster Headache Study)

Effect of L-Cysteine (Acetium™ Capsules) in Restoration of the Structure and Function of Gastric Mucosa After H. pylori

Eradication in Patients with Atrophic Gastritis. A randomized, controlled trial.

(Acetium in Treatment of Atrophic Gastritis Study)

http://www.biohithealthcare.com/fi/tutkimus/tutkimussuunnitelmia

The state-of-the-art, safe and economic

GastroPanel examination does not have any of

the following serious medical problems:

The 13C urea breath test (UBT), stool antigen test and antibody tests do not

detect atrophic gastritis which is caused by H. pylori infection or an autoimmune

disease.

The diagnosis of atrophic gastritis (AG) is important because of the risks that

associate with AG. These are the risks of gastric and oesophageal cancer and

malabsorption of vitamin B12, iron, magnesium, calcium and some drugs.

Calcium deficiency causes osteoporosis, and vitamin B12 deficiency can cause

Alzheimer’s disease, dementia, depression and polyneuropathy, as well as high

homocysteine content in the body, which in turn is thought to be an independent

risk factor for atherosclerosis, heart attacks and strokes. The absorption of

dipyridamole, some iron products and antifungals (fluconazole, itraconazole),

thyroxine and atazanavir is considerably impaired in an anacidic stomach.

APPENDIX 1

Atrophic gastritis in the gastric corpus and PPI therapy cause anacidity

(aclorhydria) of the stomach. The risk of pneumonias and, in senior citizens,

even the risk of fatal intestinal infections (such as giardiasis, malaria,

Clostridium difficile and E. coli EHEC) may increase significantly in an anacidic

stomach.

H. pylori gastritis may also develop into antral atrophic gastritis, which

increases the risk of peptic ulcer disease and gastric cancer. If both antrum and

corpus mucosa are atrophic, this condition is the highest risk for gastric cancer

known to date.

Furthermore, none of the aforementioned three H. pylori tests provides any

information on excessive gastric acid secretion (high acid output), which in

patients with gastro-oesophageal reflux disease may cause complications of

this disease in esophagus. Such complications are often asymptomatic and

include ulcerative oesophagitis and Barrett’s oesophagus, which may lead to

oesophageal cancer if left untreated. In addition, the 13C urea breath test and

stool antigen test may give up to 50 % false negative results if the patient has

a) atrophic gastritis b) MALT lymphoma or c) bleeding peptic ulcer disease or

d) if the patient is currently receiving antibiotics or PPIs.

APPENDIX 1, continues

Thank you very much for your attention!