jurnal digestif

8/18/2019 Jurnal Digestif

1/19

Features of gastritis predisposing to gastric adenoma and early

gastric cancer

Abstrak

Helicobacter pylori gastritis is a risk factor for the development of gastric cancer. The

results of several studies indicate that gastric adenomas, which are considered premalignant

lesions, may also be associated with H pylori gastritis. However, it is not clear whether there

are different patterns of gastritis in these patients compared with patients with gastric cancer

or patients with H pylori gastritis alone. Therefore, this study was designed to investigate the

patterns of gastritis in these three groups of patients.

METHODS

The histological features of gastric mucosa at a distance from the tumour wereanalysed prospectively in 118 patients with gastric adenoma (mean age, 71.8 female to male

ratio, ! " #$. %n addition, for every patient with H pylori associated gastric adenoma an age

and se& matched control patient with either H pylori associated early gastric cancer of the

intestinal type or H pylori gastritis only was investigated.

RESUTS

'nly ! patients ().*+$ with gastric adenoma were infected with H pylori. %n the

remaining patients, complete atrophic gastritis predominated. %n those patients with adenoma

and H pylori infection, the gastritis was similar to that seen in patients with early gastric

cancer (median score, for activity and degree of gastritis in the antrum and corpus$

intestinal metaplasia was common to both groups. These two groups differed significantly

from patients with H pylori gastritis only (median grade and activity of gastritis, 1 in antrum

and corpus$, in whom intestinal metaplasia was rare.

!O"!US#O"S

%t appears that gastric adenomas and gastric intestinal cancer arise by analogous

mechanisms. However, owing to severe atrophic gastritis and a lower incidence of H pylori,

adenomas do not appear to be definite precursor lesions for gastric cancer.

1


2/19

%t is known that infection with Helicobacter pylori always causes chronic active

gastritis. %nfection with the bacterium provokes invasion of the mucosa by

lymphocytes-plasma cells (a marker for the grade of gastritis$, and neutrophils (a marker for the activity of gastritis$. %n addition to these diffuse parameters, multifocal features such as

intestinal metaplasia, atrophy, and lymphoid follicles may also be found in association with H

pylori infection.1

or gastric cancer of the intestinal type, /orrea suggested a human model of carcinogenesis.

He postulated that hyperproliferation caused by H pylori gastritis is the starting point of a

se0uence leading to gastric cancer. This hyperproliferation may then initiate 23 alterations.

The mutation of several antigens, such as 4ewis a and carcinoembryonic antigen, suppressor

genes, such as p)5, or oncogenes, such as c6myc, 3/- catenin, or ras, might be associated

with the evolution from normal gastric mucosa to carcinoma. These changes are representedhistopathologically by superficial gastritis leading to multifocal atrophy, intestinal metaplasia

and, finally, dysplasia-cancer. %t has also been reported that cancers may develop via gastric

adenomas# hence6as for the carcinogenesis of colorectal carcinomas)6adenomas have been

regarded as premalignant lesions.#

However, data on gastric adenomas are still very sparse and, surprisingly, the incidence of

gastric adenoma is much lower than that of gastric carcinoma.!67 Hence, most gastric cancers

do not develop via adenomas. %n addition, in contrast to gastric cancer, little is known about

the features of gastritis associated with gastric adenomas. This background prompted us to

conduct a study, first to investigate the histopathological features of gastric adenomas6in particular the surrounding mucosa66 and then to compare these findings with the patterns of

2


3/19

gastritis in patients with early gastric cancer of the intestinal type and patients with gastritis

alone.

$AT#E"TS A"D METHODS

9e analysed retrospectively all gastric adenomas investigated histopathologically at

the pathological institute of :ayreuth between 1*!* and 1**!. or inclusion in the study,

additional biopsies from the antrum and corpus mucosa at a distance from the tumour also

had to be available a total of 118 patients met these criteria. 3t the time of diagnosis, the

patients; mean age was 71.8 years (atching was effected blind to the results of the histopathological

e&aminations with the e&ception of H pylori status.

3


4/19

araffin wa& embedded samples were sectioned and stained with haemato&ylin and eosin and

the 9arthin6


5/19

intestinal metaplasia in the antrum or corpus was more fre0uently present in the two groups

with gastric tumours than in the group with gastritis only. The presence of intestinal

metaplasia in the antrum was most prominent in the group with gastric cancer, whereas in the

corpus this feature was more often present in patients with gastric adenoma. However, these

differences between the two groups were not significant (tables 1 and $.D#S!USS#O"

'ur data show that the proportion of patients with gastric adenoma and H pylori

infection is lower than that reported for patients with early gastric cancer. 'nly ).*+ of the

patients with gastric adenoma were infected with the organisms, whereas our own previously

published data, in addition to data from others, show incidence rates of H pylori infection of

around 86*+ for those with early gastric cancer.8611 However, when H pylori was

detected, gastritis parameters were similar in patients with gastric adenoma and early gastric

intestinal cancer. %n both groups, H pylori gastritis was comparatively severe in the antrum

and the corpus, and intestinal metaplasia was a common finding.

%n light of the fact that both H pylori infection and gastric adenomas are thought to be

premalignant lesions in a se0uence leading to gastric cancer, why was H pylori infection in

the group of patients with gastric adenoma less fre0uent than e&pectedD %f there really is a

se0uence of H pylori gastritis 6 metaplastic changes 6 adenoma 6 carcinoma, one would

e&pect to find at least as many H pylori infected patients with a EpremalignantE adenoma as

with gastric cancer.

However, in those patients with gastric adenoma but no concomitant H pylori, either body

predominant atrophic gastritis (6 #5+$ or gastritis showing the typical features of an earlier H pylori infection (6 7+$ was diagnosed. These data are in agreement with other reports

5


6/19

showing a similarly high fre0uency of complete atrophy in the adenoma bearing stomach.1

15 Therefore, the incidence of complete atrophic gastritis in patients with gastric adenoma is

much higher than in the general population1# or in populations with confirmed gastric

cancer.8 9e now know that in some cases infection with H pylori can induce severe

inflammation with destruction of the corpus glands (Epre6atrophic stageE$, which finally leadsto complete atrophy of the corpus mucosa (Eatrophic stageE$.1) 1! This stage of atrophy with

loss of acid production does not favour the growth of H pylori.17 Thus, in some cases, H

pylori may no longer be detectable, even though it initially induced the mucosal damage.

Hence, we speculate that the high incidence of atrophic gastritis in the group of patients with

gastric adenoma might reflect a Eburned outE mucosa as a response to long lasting severe H

pylori gastritis. %n addition, the remaining 7+ of patients with neither H pylori nor atrophic

gastritis showed the typical features of gastritis often found after eradication of the

organism.18 1*

However, when H pylori was present the gastritis resembled the gastric cancer phenotype of H pylori gastritis (that is, severe gastritis in the antrum and corpus, high percentage of

intestinal metaplasia$. 1 Therefore, it could be speculated that this pattern of gastritis

initially induced by H pylori causes both gastric adenoma and gastric cancer. However, the

observation that many more patients develop cancer rather than adenoma,! 7 and that a

comparatively high proportion of patients with gastric adenoma develop complete atrophy,

whereas most patients with early gastric cancer still have active H pylori gastritis, remains to

be clarified. 3 possible e&planation could be that adenomas are relatively slow growing

neoplasms so that the surrounding mucosa more often reaches an Eend stageE of atrophic

gastritis. %n contrast, cancers progress more rapidly and fewer patients will reach complete

atrophic gastritis before detection.

'f interest in this regard are data published by Hattori from Fapan. 'n analysing gastric

microcarcinomas of the intestinal type (diameters G) mm$ he found no precursor lesions in

the tumour margins, and concluded that intestinal metaplasia, dysplasia, and carcinoma arise

coincidentally. This implies that no precursor is present for either of them, which is in direct

contradiction to the /orrea model postulating a cascade ending in gastric cancer. 'n the basis

of Hattori;s data, it might be speculated that severe gastritis caused by H pylori infection

leads to a constant cellular stress. 3s a result, the following mechanisms may be triggered"

the cells of the mucosa undergo apoptosis leading to atrophy, or they become metaplastic

(intestinal metaplasia$, or6in the worst case66 dysplastic. Hence, in contrast to colorectal

cancer, we do not believe that there is a se0uence of events beginning with gastritis leading to

gastric adenoma and finally ending in gastric cancer of the intestinal type. %n our opinion,

mucosal stress is reflected by epithelial alterations such as metaplasia and-or atrophy, which

may therefore be regarded as markers for an increased risk of gastric cancer. This does not

mean that malignant growth derives from metaplasia-atrophy, making the latter a condition

for the development of the former. The reason why far more cancers develop in active severe

H pylori gastritis and not in complete atrophic gastritis, which, in contrast, is found

disproportionately more often in association with gastric adenomas, might be the fact that

active inflammation leads to a series of changes that are probably involved in carcinogenesis"

6


7/19

the ammonia produced by H pylori,5 increased cell proliferation,# ) increased production

of free o&ygen radicals,! and the increased production of nitric o&ide7 may all trigger

mutations in the stem cells. The development of intestinal metaplasia and-or atrophy might

therefore be a physiological reaction of the gastric mucosa aimed at protecting itself from the

constant stress caused by H pylori. %f this theory were correct, one would e&pect adenomaswith active H pylori associated gastritis in the surrounding mucosa to show an average higher

grade of dysplasia. However, in our study only low grade dysplasia was found in adenomas,

perhaps because most of the adenomas under investigation were not removed in total to check

for areas with high grade dysplasia. %t would be interesting to investigate whether adenomas

with higher grades of dysplasia are indeed associated to a greater e&tent with active gastritis,

similar to that found in early gastric cancers.

7


8/19

References

1 i&on >, ?ento >, Iardley FH, et al. /lassification and grading of gastritis" the updated

olecular pathology of gastric carcinoma" current state of research. athologe

1"576#5.

# >orson :/, iehlke eining 3, et al. Histological diagnosis of Helicobacter pylori

gastritis is predictive of a high risk of gastric carcinoma. %nt F /ancer 1**775"8576*.

* iocca , 4uinetti ', @illani 4, et al. High incidence of Helicobacter pylori coloniKation in

early gastric cancer and the possible relationship to carcinogenesis. BurF ?astroentero-

Hepatol 1**5)"68.

1 Jikuchi


9/19

18 @alle F, eining 3, :ayerdorffer B, >iller , et al. ?astric carcinoma risk inde& in patients

infected with Helicobacter pylori. @irchows 3rch 1**8#5"51161#.

1 , Bidt


10/19

Fitur gastritis predisposisi adenoma lambung dan kanker

lambung dini

A%STRA&

Helicobacter pylori gastritis merupakan faktor risiko untuk pengembangan kanker lambung. Hasil beberapa penelitian menunLukkan bahwa adenoma lambung, yang dianggap

lesi pra6ganas, Luga dapat dikaitkan dengan H pylori gastritis. 2amun, tidak Lelas apakah ada

pola yang berbeda dari gastritis pada pasien ini dibandingkan dengan pasien dengan kanker

lambung atau pasien dengan H pylori gastritis sendiri. 'leh karena itu, penelitian ini

dirancang untuk menyelidiki pola gastritis di tiga kelompok pasien.

METODE

itur histologis mukosa lambung pada Larak dari tumor dianalisis secara prospektif

pada 118 pasien dengan adenoma lambung (usia rata6rata, 71,8 wanita untuk rasio laki6laki,

!" #$.


11/19

Hal ini diketahui bahwa infeksi Helicobacter pylori selalu menyebabkan gastritis

kronis aktif. %nfeksi bakteri memprovokasi invasi mukosa oleh sel limfosit - plasma (penanda

untuk kelas gastritis$, dan neutrofil (penanda untuk kegiatan gastritis$. utasi beberapa antigen, seperti 4ewis dan antigen

/arcinoembryonic, gen penekan, seperti p)5, atau onkogen, seperti c6myc, 3/ - catenin,

atau ras, mungkin terkait dengan evolusi dari mukosa lambung normal karsinoma . erubahan

ini diwakili oleh histopatologi gastritis superfisial menyebabkan atrofi multifokal, metaplasia

usus dan, akhirnya, displasia - cancer. %ni Luga telah melaporkan bahwa kanker dapat

berkembang melalui adenomas# lambung maka6seperti untuk karsinogenesis kolorektal

carcinomas)6adenoma telah dianggap sebagai lesions.# premalignant

2amun, data adenoma lambung masih sangat Larang dan, mengeLutkan, insiden adenoma

lambung Lauh lebih rendah dibandingkan dengan carcinoma.!67 lambung 'leh karena itu,

kanker yang paling lambung tidak berkembang melalui adenoma.


12/19

$AS#E" DA" METODE

Jami menganalisis secara retrospektif semua adenoma lambung diselidiki

histopatologi di lembaga patologis :ayreuth antara tahun 1*!* dan 1**!. Nntuk dimasukkan

dalam penelitian ini, biopsi tambahan dari antrum dan korpus mukosa pada Larak dari tumor

Luga harus tersedia total 118 pasien yang memenuhi kriteria tersebut. ada saat diagnosis,

usia rata6rata pasien adalah 71,8 tahun (


13/19

arafin lilin tertanam sampel dipotong dan diwarnai dengan hematoksilin dan eosin dan noda

9arthin6


14/19

metaplasia usus di antrum yang paling menonLol dalam kelompok dengan kanker lambung,

sedangkan di corpus fitur ini lebih sering muncul pada pasien dengan adenoma lambung.

2amun, perbedaan6perbedaan antara kedua kelompok tidak signifikan (tabel 1 dan $.

$EM%AHASA"

ata kami menunLukkan bahwa proporsi pasien dengan adenoma lambung dan infeksi

H pylori lebih rendah dari yang dilaporkan untuk pasien dengan kanker lambung dini. Hanya

),*+ dari pasien dengan adenoma lambung terinfeksi dengan organisme, sedangkan data

kami sendiri diterbitkan sebelumnya, selain data dari orang lain, tingkat insiden menunLukkan

infeksi H pylori sekitar 86*+ bagi mereka dengan awal cancer.8 lambung 611 2amun,

ketika H pylori terdeteksi, parameter gastritis adalah serupa pada pasien dengan adenoma

lambung dan kanker usus lambung awal. ada kedua kelompok, H pylori gastritis adalah

relatif parah di antrum dan korpus, dan metaplasia intestinal merupakan temuan umum.

>engingat fakta bahwa kedua infeksi H pylori dan adenoma lambung dianggap lesi pra6

ganas dalam urutan yang mengarah ke kanker lambung, mengapa infeksi H pylori padakelompok pasien dengan adenoma lambung lebih Larang dari yang diharapkanD Fika memang

ada urutan H pylori gastritis 6 perubahan metaplastic 6 adenoma 6 karsinoma, orang akan

berharap untuk menemukan setidaknya sebanyak H pylori terinfeksi pasien dengan

EpremalignantE adenoma seperti kanker lambung.

2amun, pada pasien dengan adenoma lambung tapi tidak bersamaan H pylori, baik tubuh

gastritis dominan atrofi (6 #5+$ atau gastritis menunLukkan fitur khas infeksi H pylori

sebelumnya (6 7+$ didiagnosis. ata ini sesuai dengan laporan lain yang menunLukkan

frekuensi sama tinggi atrofi lengkap dalam bantalan adenoma stomach.1 15 'leh karena itu,

keLadian gastritis atrofi lengkap pada pasien dengan adenoma lambung Lauh lebih tinggi

daripada di population1# umum atau pada populasi dengan dikonfirmasi cancer.8 lambung

Jita sekarang tahu bahwa dalam beberapa kasus infeksi dengan H pylori dapat menyebabkan

14


15/19

peradangan berat dengan kerusakan kelenLar corpus (Etahap pra6atrofiE$, yang akhirnya

mengarah untuk menyelesaikan atrofi mukosa corpus (Etahap atrofiE$ .1) 1! tahap ini atrofi

dengan hilangnya produksi asam tidak mendukung pertumbuhan H pylori.17 demikian,

dalam beberapa kasus, H pylori mungkin tidak lagi terdeteksi, meskipun awalnya disebabkan

kerusakan mukosa. 'leh karena itu, kita berspekulasi bahwa tingginya insiden gastritis atrofi pada kelompok pasien dengan adenoma lambung mungkin mencerminkan EterbakarE mukosa

sebagai respon terhadap tahan lama parah H pylori gastritis. enurut pendapat kami, stres mukosa tercermin perubahan epitel seperti metaplasia dan -

atau atrofi, yang karenanya dapat dianggap sebagai penanda untuk peningkatan risiko kanker

lambung. %ni tidak berarti bahwa pertumbuhan ganas berasal dari metaplasia - atrofi,

membuat kondisi kedua untuk pengembangan mantan. 3lasan mengapa Lauh lebih kanker

berkembang di aktif parah gastritis H pylori dan tidak gastritis atrofi lengkap, yang, berbeda,

ditemukan secara tidak proporsional lebih sering dalam hubungan dengan adenoma lambung,

mungkin kenyataan bahwa peradangan aktif menyebabkan serangkaian perubahan yang

mungkin terlibat dalam karsinogenesis" amonia yang diproduksi oleh H pylori, 5 meningkat

proliferasi sel, # ) peningkatan produksi radikal oksigen bebas, ! dan peningkatan

produksi o&ide7 nitrat mungkin semua mutasi memicu dalam sel induk. erkembangan

metaplasia usus dan - atau atrofi karena itu mungkin reaksi fisiologis mukosa lambung yangdituLukan untuk melindungi diri dari stres konstan yang disebabkan oleh H pylori. Fika teori

15


16/19

ini benar, orang akan berharap adenoma dengan aktif H pylori gastritis terkait dalam mukosa

sekitarnya untuk menunLukkan nilai rata6rata yang lebih tinggi dari displasia. 2amun, dalam

penelitian kami hanya kelas displasia rendah ditemukan pada adenoma, mungkin karena

sebagian besar adenoma diselidiki tidak dihapus secara total untuk memeriksa daerah dengan

kelas tinggi dysplasia. 3kan menarik untuk menyelidiki apakah adenoma dengan nilai yanglebih tinggi dari displasia memang terkait dengan tingkat yang lebih besar dengan gastritis

aktif, mirip dengan yang ditemukan pada kanker lambung dini.

16


17/19

Referensi

1 i&on >, ?ento >, Iardley FH, et al. Jlasifikasi dan grading gastritis" sistem olekul patologi karsinoma lambung" keadaan saat ini penelitian. athologe1 " 576#5.

# >orson :/, iehlke eining 3, et al. iagnosis histologis Helicobacter pylori

gastritis adalah prediksi risiko tinggi kanker lambung. %nt F Janker 1**7 75" 8576*.* iocca , 4uinetti ', @illani 4, et al. Tingginya insiden Helicobacter pylori kolonisasi pada

kanker lambung dini dan kemungkinan hubungan dengan karsinogenesis. BurF ?astroentero -

Hepatol 1**5 )" 68.

1 Jikuchi iller , et al. 4ambung indeks risiko karsinoma pada pasien

terinfeksi Helicobacter pylori. @irchows 3rch 1**8 #5" 51161#.

1 , Bidt


18/19

# /ahill F,


19/19

Daftar Pustaka

/itation style" 33 !th 6 3merican sychological 3ssociation, !th Bdition

>eining, 3., iedl, :., M . ($. eatures of gastritis predisposing to gastric

adenoma and early gastric cancer. Fournal of /linical athology, ))(1$, 7765. etrieved

from http"--search.pro0uest.com-docview-1*717!)1)DaccountidO)7#

19

jurnal digestif

Documents