The methods which require endoscopy for the examination of the gastric muco
sa are called invasive (direct) methods. Several tests can be performed on
the gastric mucosa obtained by endoscopy: Rapid urease test, histology, sme
ar (cytology), culture and polymerase chain reaction. A combination of at l
east two tests with high sensitivity and specificity is recommended for cli
nical trials, and, when possible, for clinical management of patients. In c
linical practice the invasive methods should be carried out only in those p
atients to be treated with eradication regimes. All invasive methods rely o
n gastric biopsy samples. Therefore, the specimens should be taken under op
timal conditions. Several factors guide the sire and the number of biopsy s
pecimens for identification of Helicobacter pylori infection. In pre-treatm
ent diagnosis, the biopsies should be taken from the distal antrum (2 cm fr
om the pylorus). The number required depends on the diagnostic method used:
in Helicobacter pylori eradicated patients the same number of biopsies for
histology and culture should be taken from the antrum and corpus. The sens
itivity and specificity of the Rapid Iii-ease test val ies from 80-90% the
results al-e known very quickly and the cost is very low. The maximal accur
acy of histology is obtained with: an optimal specimen processing, an adequ
ate staining and an experienced observer This method of biopsy processing f
acilitates the identification of Helicobacter pylori which is commonly loca
ted on the superficial and foveolar epithelium. Sensitivity depends on the
observer's experience and the extent of biopsy sampling. In general, the hi
stological method has a sensitivity and specificity of 90-95%. In patients
treated by proton pump inhibitors, antibiotics or bismuth salts two-four we
eks prior to biopsy, the bacteria may he restricted to the corpus or fundus
. Culture is strictly indicated in patients after failure of two or more er
adication regimens to test for susceptibility and resistance. Specificity i
s 100% and sensitivity depends on the experience and interest of the microb
iologist. The indication of polymerase chain reaction is only for research,
specially, in molecular epidemiology and for fingerprinting.