Gastrin, the enterochromaffinlike cell, and gastric tumors

1264

GASTROENTEROLOGY

CORRESPONDENCE

can speculate with

that it is difficult

immunostaining

monoclonal ture

with

antibody

because

by progressive

problem,

to identify

proliferating

of the destruction

inflammatory

antibody

identifying trating

and anti-type

IV collagen into acinar

macrophages

ity of acinar released.

may possibly

These findings

occurring

in acinar

suggest

antibody,

cells,

that apoptosis

cells during

this mono-

resulting

from

term

of patients

in

activ-

KENJIRO MATSUNO Kumamoto Universig Medical School Kumamoto,Japan 1. Frey CF, Bradley III EL, Berger HG. Progress in acute pancreatitis. Surg Gynecol Obstet 1988; 167:282-286. 2. Walker NI. Untrastructure of rat pancreas after experimental duct ligation. I. The role of apoptosis and intraepithelial macrophages in acinar cell deletion. Am J Pathol 1987; 126:439-45 1. 3. Medich DS, Lee TK, Melhem MF, Rowe MI, Schraut WH, Lee KK. Pathogenesis of pancreatitis sepsis. Am J Surg 1993; 165:46-52. 4. Sameshima H, lkei S, Mori K, Yamaguchi Y, Egami H, Misumi M, Moriyasu M, Ogawa M. The role of tumor necrosis factor-a in the aggravation of cerulein-induced pancreatitis in rats. Int J Pancreato1 (in press). 5. Yamaguchi Y, Matsuno K, Goto M, Ogawa M. In situ kinetics of acinar cell, duct, and inflammatory cells in duct ligation-induced pancreatitis in rats. Gastroenterology 1993; 104: 1498- 1506. 6. Goto M, Matsuno K, Yamaguchi Y, Ezaki T, Ogawa M. Proliferation kinetics of macrophage subpopulations in a rat experimental pancreatitis model. Arch Histol Cytol 1993;56:75-82.

was beneficial

Crohn’s and

disease

surgical

oxygen other had ing,

in treating for 8 years.

has been successfully

not

responded

to medical

had

complete

were

completely

whose

without

recurrence

sustained

oxygen.’ remission

she had become and the extent

carcinomas.’

hitherto

inclusion

criterion

Since

then,

each,

20 sessions

each

completed

April

treated

disease reheal-

and

surgery

report,

since starting

each)

with

24, 1990. She has been asymptomatic

and but

treatment

nomas.’

courses

of

the last course ever since,

underestimated.

Cell,

excludes

of which

reported

cell-derived

tumor

(ECL)

may

et al.,’ was heavily

research

group

by Rindi

their

that

the tumor

thoroughly

cells,”

histamine

This could staining

(negative).’ study

that

serotonin

even more

tumors

and thus

et al. report

carcinomas

have been performed

This becomes

do metastasize

Rindi

resemble

cells in these tumors and

classified

of

cells compared

study

have been of great

(positive)

shows

evaluation of the secretory

neuroendocrine

but it would

immuno-

for a long time and

microscopic

5 In their

the malignant

cell characteristics. Sevier-Munger the present

without

cells in the neuroendocrine

examine

chemistry

or elec-

that the work from the

the appearance

counterparts.

carci-

to in the paper acd Solcia4

in malignant

normal

carci-

of enterochro-

by Creutzfeldt

surprising

because

as

gastric

cells in 40% of gastric

et al.,’ electron

is different

with

differentiated

as has been known

is difficult

the

classified

immunohistochemistry

was performed

Moreover,

tumors

previously

the finding

criticized

It is thus rather

tumors

be neuroendoendocrine

histamine

the

Unfortunately,

type.‘,’ This study, not referred

also for not including tron microscopy.

neuroendocrine

poorly

previously

et al. from

and neuroendocrine

(“tumors

some

by Rindi

noids

that gastric

been

tumors”‘)

of the diffuse

Solcia

shows

We have

maffinlike nomas

by Rindi

carcinoids

for the study

interest

to

for ECL

by combining immunohisto-

important

because

as ECL cell carci-

are to be considered

as malignant

tumors.’ The most remarkable only

benign

types

statement

of gastric

hypergastrinemia,

implying

tumors. contrary,

In our opinion, indicate

the data compilation 1. In the discussion linger-Ellison

render on gastric syndrome,

neuroendocrine

obtained

actually

tumors.

by Rindi

to

gastric

et al., on the

may have an important

In addition,

some questions ECLomas Rindi

that

are related

does not play any impor-

of malignant

that gastrin

et al, is the claim

cell carcinoids

that gastrin

the results

of these

by Rindi

ECL

tant role in the tumorigenesis

in the induction

with pretreat-

has had two additional

(27 and 26 sessions

et

the longest

had been only 2.5 months, compared

two

and were

by Nelson

after completing

asymptomatic

the patient

in an-

Crohn’s

40 sessions

of her disease was minimal

oxygen

to surgery

after

in 24 months in our patient

hyperbaric

but not complete

The patient

have

endocrine

carcinomas,

the article

argyrophil

This paper

probably gastric

interest

on gastric

“protoendocrine

medical

report,

Of the six patients

At the time of our initial

essentially

hyperbaric

that

after

for 3 months.3

al. had no recurrence hyperbaric

healed

hyperbaric

and cutaneous

perianal

therapy.3

healing

concern-

to conventional

Since

by Lavy et al., two had considerable two

perineal

used as an adjunct

and in six patients

patients

ment.

severe

read with

group

confirmed

in 1989,’ in whom

that had been refractory

therapies

patient’

ported

We have Solcia

granules

in this journal

III, M.D.

Dear Sir:

these

Dear Sir: reported

number

study.

Gastrin, the Enterochromaffinlike and Gastric Tumors

histochemistry.

Hyperbaric Oxygen and Perineal Crohn’s Disease: A Follow-up

ing a patient

further

and long-

in a small

Brady CE, Cooley BJ, Davis JC. Healing of severe penneal and cutaneous Crohn’s disease with hyperbaric oxygen. Gastroenterology 1989;97:756-760. Nelson EW, Bright DE, Villar LF. Closure of refractory perineal Crohn’s lesion. Integration of hyperbaric oxygen into case management. Dig Dis Sci 1990;35: 156 1- 1565. Lavy A, Melamed Y, Weiss G, Eidelman S. Hyperbaric oxygen heals perianal fistulas in Crohn’s disease (abstr). Gastroenterology 1992; 102:A65 1.

pancreatitis

results

but the short-

that have been achieved

for

San Antonio, Texas 782X4-7878

Depatiment of Anatomy II

oxygen

deserves

disease,

on

not recommended

Universig of Texas Health Science Center at San Antonio

cytokines

Department of Surgev II

follow-up

Crohn’s

effects

and was last seen in clinic

is certainly

CHARLES E. BRADY

YASUO YAMAGUCHI MATARO GOT0 MICHIO OGAWA

like to share some long-term

oxygen

No. 4

Division of Gastroenterology

in the rat.

I would

treatments,

use in perineal beneficial

is not the only event

duct ligation-induced

further

May 5, 1993. Hyperbaric

1E). Infil-

the proliferative

resulting

has not required routine

architec-

overcome

cells (Figure

modulate

cells as well as duct

To

with anti-BrdU

BrdU incorporation

cells

(BrdU)

of acinar

response.

we used double-immunostaining

clonal

acinar

anti-5-bromo-2’-deoxyuridine

Vol. 105.

role

inconsistencies

in

unanswered.

in patients

et al. mention

with the Zoltwo

patients

October

CORRESPONDENCE

1993

with

gastric

neoplasia

ECLoma type

alone

may induce

Rindi

et al. describe

two were

without

I (MEN

evidence

six neuroendocrine

in the antrum,

and two in the body-fundus.’ one of these tumors whereas

gastrin

of course

patients

with

Rindi

et al. define seem

meaning

used

that

hypergastrinemia

therefore

is supported

for the trophic

and gastric

carcinoids

study

the

possible

independent

carcinogenesis

is a continuous

mutations.” conceivable

cell in gastric

cell

chronic

gastric

atro-

carcino-

types

of ECL

neuroendocrine

throughout

and multistep

In other

words,

It should

into

mutations

cells become could

of the ECL

that

including in the

hypergastrinemia,

it is

gastrin

also be recalled

which

pro-

account

process

although

without

all mutated

that

individ-

the carcinogenetic taken

cell

carci-

Are they of the opinion

inde-

that histamine

be an important

ce11,13 which

factor

normally

pro-

Waldum HL. Are diffuse gastric carcinomas neuroendocrine tumours ECL-omas? Eur J Gastroenterol Hepatol 199 1;3:863865. 4. Creutzfeldt W, Solcia E. Are diffuse gastric carcinomas neuroendocrine tumours ECL-omas? Eur J Gastroenterol Hepatol 199 1;3:862-863. 5. D’Adda T, Corleto V, Pilato FP, Baggi MT, Robutti F, Delle Fave G, Bordi C. Quantitative ultrastructure of endocrine cells of oxyntic mucosa in Zollinger-Ellison syndrome. Gastroenterology 1990; 99: 17-26. 6. Simonsson M, Eriksson S, H%kanson R, Lind T, L0nroth H, Lundell L, O’Connor DT, Sundler F. Endocrine cells in the human oxyntic mucosa. A histochemical study. Stand J Gastroenterol 1988;23: 1089- 1099. 7. Brenna E, Waldum HL. Trophic effect of gastrin on the enterochromaffin like cells of the rat stomach: establishment of a dose response relationship. Gut 1992;33: 1303- 1306. 8. Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P, Calam J. Antral Helicobacter pylori, hypergastrinaemia, and duodenal ulcers: effect of eradicating the organism. Br Med J 1989;299: 1504- 1505. and cancer: different perspectives on 9. Sporn MB. Carcinogenesis the same disease. Cancer Res 199 1;5 1:62 15-62 18. 10. Grigioni WF, Caletti GC, Gabrielli M, Marrano D, Villanacci V, Mancini A. Gastric carcinoids of ECL cells. Pathological and clinical analysis of eight cases. Acta Pathol Jpn 1985;35:361-375. 11. Fraser RA, Simpson JG. Role of mast cells in experimental tumour angiogenesis. In: Development of the vascular system. Ciba Foundation symposium 100. London: Pitman, 1983: 120131. 12. Marks RM, Roche WR, Czerniecki M, Penny R, Nelson DS. Mast cell granules cause proliferation of human microvascular endothelial cells. Lab Invest 1986;55:289-294. Lancet 199 1;337:6 14. 13. Waldum HL. Exploiting engiogenesis. 14. HAhanson R, BOttcher G, Ekbland E, et al. Histamine in endocrine cells in the stomach: a survey of several species using a panel of histamine antibodies. Histochemistry 1986;86:517. 15. Waldum HL, Petersen H, Brenna E. Gastrin and gastric cancer. Eur J Gastroenterol Hepatol 1992;4:80 l-8 1 1. Reply.

Contrary

et al. shows

role in gastric

tumorigenesis.’

role of gastrin

supports

previous

tumorigenesis

that the ECL cell The study

in this tumorigenesis.’ studies

also

There-

on the role of the ECL

and the role of gastrin

in this pro-

the inclusion

used

study’

in our

gastric diffuse

type,

suggestive

HELGE L. WLADUM, PH.D. ARNE K. SNADVIK, PH.D. EILIV BRENNA, PH.D. Department of Medicine Universi~ Hospital N-7006

Trondkim, Norway

1. Rindi G, Luinetti 0, Cornaggia M, Capella C, Solcia E. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 1993; 104:994-1006. 2. Waldum HL, Haugen OA, lsaksen C, Mecsei R, Sandvik AK. Are diffuse carcinomas neuroendocrine tumors (ECL-omas)? Eur J Gastroenterol Hepatol 199 1;3:245-249.

criteria

did

carcinomas

not

which

study

only

a single

histochemical

dant

with

or with

(NEC)

all diffuse

cells. cancers,

In

the

ferentiation,

junctional

systems,

etc.) were

Concerning

differentiation,

that poor

fuse cancers

and NECs,

d@entiation,

which

of “poorly

in our diagnostic and ultrastructurally

of NECs routine

tumors, (mu-

surface

dif-

prevalent

at least when

over

the tumor

differentiated

NECs

from

tumors” in both poor

and very few other are further

for possible

that we or other so many

largely

is to be distinguished

is typical

all of which

fail to diagnose

315

histologicalbnrcture, present

chemically

we do not believe

differof abun-

differentiation luminal

of

differen-

sampled.“d

the histology

must be outlined

features

remaining

signs of exocrine pepsinogens,

endocrine

was also

coexistence

antigens,

was extensively

patterns

This

signs of exocrine

mucinlike

those suggesting

histological

(carcinoid)

In

83 cases of

signs of endocrine

tin granules,

growth

carcinomas.”

(NEC).

only minor

we

differentiated

and ultrastructural

or without

undifferentiated

including

Sandvik, tumors

including

case with

i.e., widespread

in the absence

“poorly

carcinoma

an endocrine tiation

those cancers,

the only case showing tumor,

Waldum, endocrine

may be neuroendocrine

of 316 gastric

showed

of Drs.

for gastric

exclude

for neuroendocrine

entiation,

cess. I5

to the assumption

and Brenna,

fact, a parallel

the study by Rindi

an important

this study

Therefore,

that

I4

an important

supports fore,

they do not men-

affect

malignant

do not have

angiogenesis,“.‘*

histamine.

could

ECL

may occur

immediately.

In conclusion, plays

they

that

in the tumorigenesis duces

excluding

dependent.’

that

promotes

of neuroendocrine

hypergastrinemia.’

the more

uals are gastrin

pendent

a view

on the concentration

However,

clearly

cess? It seems

hardly

the importance

in the ECL cell in normogastrinemic

ECL cells naturally

of 60

as above

hypergastrinemia.

that

starting

value.’

value

tumorigenesis,’

experiments

carcinomas.

are not gastrin

multiple

gastrin

hypergastrinemia

or H. pylon’ infection

and

all tumors

upper

in gastric

H. pylon’ also induces

et al. claim

nomas

as twice the normal

et al.’ argue that Helicobuctetpyloti could

only by inducing

Rindi

as well as in which

role in the development

is no existing

genesis

it

effect of gastrin.’

Rindi

play an important

phic gastritis

mucosa,

the localization

seem to emphasize

by animal

In the Discussion

there

in only four

effect specifically

to know

hyperplasia

that

cell hy-

in the oxyntic

they defined

They

that

was determined

a normal

57 pmol/L.

tion

argyrophil

has a trophic

hypergastrinemia

to have

carcinomas

zone,

3 it is apparent

with

exclusively

of moderate range

Table

in blood

argyrophil

of which

was determined.

They

that

carcinomas

have been of interest

gastrin

pg/mL,

From

gastrin

on the ECL cells located of the tumor

3.

endocrine

hypergastrinemia

two in the transitional

was accompanied

of the six cases.’ Because would

that

such tumors.

located

perplasia,

of multiple

I), indicating

1265

experienced

as suggested

investigated NEC

nature.

pathologists by Waldum

it dif-

#tologic tumors, histoThus, really et al. In