jurnal digestif
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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$, in whom intestinal metaplasia was rare.
!O"!US#O"S
%t appears that gastric adenomas and gastric intestinal cancer arise by analogous
mechanisms. However, owing to severe atrophic gastritis and a lower incidence of H pylori,
adenomas do not appear to be definite precursor lesions for gastric cancer.
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%t is known that infection with Helicobacter pylori always causes chronic active
gastritis. %nfection with the bacterium provokes invasion of the mucosa by
lymphocytes-plasma cells (a marker for the grade of gastritis$, 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
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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.
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araffin wa& embedded samples were sectioned and stained with haemato&ylin and eosin and
the 9arthin6
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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
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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"
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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.
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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
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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
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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,
!" #$.
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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.
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$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 (
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arafin lilin tertanam sampel dipotong dan diwarnai dengan hematoksilin dan eosin dan noda
9arthin6
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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
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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
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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.
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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#.
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# /ahill F,
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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#
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