A Case of Zollinger-Ellison Syndrome whose Pancreatic ...

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Jap. J. Clin. Oncol. 1978, 8(1), 75-89 A Case of Zollinger-Ellison Syndrome whose Pancreatic Tumor Produced Multiple Hormones and a Review of 48 Cases Reported in the Japanese Literature HiROSHI TAKAMI, M.D., KEN YAMAGUCHI, M.D.*, KAORU ABE. M.D.*, ISAMU ADACHr, M.D.*, SABURO ARAI, M.D.*, TORU KAMEYA, M.D.*, KATSUMI YAMACHIKA, M.D.**, MASAO TASHIRO, M.D., YORIO NAKAGAWA, M.D. and OSAHIKO ABE, M.D. Departments of Surgery and Pathology, Kelo University School of Medicine, Tokyo, Japan * Endocrinology and Pathology Divisions, National Cancer Center Research Institute, Tokyo, Japan **Yamachika Hospital, Kanagawa, Japan Abstract A 46-year-old man developed a peptic ulcer disease and a diagnosis of Zollinger-Ellison Syndrome was strongly suspected following gastric acid stu- dies. Plasma gastrin level was found to be elevated. The operation revealed a pancreatic tumor localized at the pancreas tail. The resected tumor tissue was proved to contain large amounts of immunoreactive gastrin. In addition, calci- tonin, VIP and insulin were found to be present either as a result of immuno- fluorescence studies or the respective radioimmunoassays. Therefore, this was a case of a multiple hormone producing tumor of pancreas islet cell origin, and the symptoms due to gastrin hypersecretion were the main clinical features. In addition, 48 cases of Zollinger-Ellison Syndrome reported in Japanese liter- atures were reviewed. Introduction for ZES, and the number of reported cases is increasing (Wilson, 1973). Recently, Zollinger-Ellison Syndrome (ZES) is a secretin and calcium infusion tests are proved well known but rare clinical entity, which is to be a sensitive and reliable method for caused by overproduction of gastrin in tumor diagnosing ZES (Straus and Yalow, 1975). tissues, mostly in islet cell tumor of the It has become apparent that ZES is one pancreas. Since the gastrin radioimmuno- of the clinical manifestations of multiple assay became available (McGuigan, 1969; endocrine adenomatosis (MEA) type 1 Yalow and Berson, 1970), plasma gastrin (Ballard et al., 1964), and it has become levels have been used as a "tumor marker" important to examine the presence of MEA in patients with ZES and in their family Received May 1, 1978. members This work was supported in part by Grants- . , __„ in-Aid from the Ministry of Education, Science Here > we are reporting a case of ZES and Culture, the Ministry of Health and Wei- whose diagnosis was strongly suspected by fare, and Development Medical Research examining gastric acid secretion at the time Foundation for Adult Diseases, Japan. of first operation, which revealed a tumor Reprint requests: Kaoru Abe M.D., Endo- , o c a t e d a t f h e feas tai , p ost tive , crinology Division, National Cancer Center , , , , , I Research Institute, 5-1-1 Tsukiji, Chuo-ku, he was als0 exam.ned for the presence of Tokyo 104, Japan. MEA. at Pennsylvania State University on September 12, 2016 http://jjco.oxfordjournals.org/ Downloaded from

Transcript of A Case of Zollinger-Ellison Syndrome whose Pancreatic ...

Jap. J. Clin. Oncol. 1978, 8 ( 1 ) , 7 5 - 8 9

A Case of Zollinger-Ellison Syndrome whose Pancreatic TumorProduced Multiple Hormones and a Review of 48

Cases Reported in the Japanese Literature

HiROSHI TAKAMI, M.D., KEN YAMAGUCHI, M.D.*, KAORU ABE. M.D.*,ISAMU ADACHr, M.D.*, SABURO ARAI, M.D.*, TORU KAMEYA, M.D.*,

KATSUMI YAMACHIKA, M.D.**, MASAO TASHIRO, M.D.,YORIO NAKAGAWA, M.D. and OSAHIKO ABE, M.D.

Departments of Surgery and Pathology, Kelo UniversitySchool of Medicine, Tokyo, Japan

* Endocrinology and Pathology Divisions, National Cancer CenterResearch Institute, Tokyo, Japan

**Yamachika Hospital, Kanagawa, Japan

Abstract

A 46-year-old man developed a peptic ulcer disease and a diagnosis ofZollinger-Ellison Syndrome was strongly suspected following gastric acid stu-dies. Plasma gastrin level was found to be elevated. The operation revealed apancreatic tumor localized at the pancreas tail. The resected tumor tissue wasproved to contain large amounts of immunoreactive gastrin. In addition, calci-tonin, VIP and insulin were found to be present either as a result of immuno-fluorescence studies or the respective radioimmunoassays. Therefore, this wasa case of a multiple hormone producing tumor of pancreas islet cell origin,and the symptoms due to gastrin hypersecretion were the main clinical features.In addition, 48 cases of Zollinger-Ellison Syndrome reported in Japanese liter-atures were reviewed.

Introduction for ZES, and the number of reported casesis increasing (Wilson, 1973). Recently,

Zollinger-Ellison Syndrome (ZES) is a secretin and calcium infusion tests are provedwell known but rare clinical entity, which is to be a sensitive and reliable method forcaused by overproduction of gastrin in tumor diagnosing ZES (Straus and Yalow, 1975).tissues, mostly in islet cell tumor of the It has become apparent that ZES is onepancreas. Since the gastrin radioimmuno- of the clinical manifestations of multipleassay became available (McGuigan, 1969; endocrine adenomatosis (MEA) type 1Yalow and Berson, 1970), plasma gastrin (Ballard et al., 1964), and it has becomelevels have been used as a "tumor marker" important to examine the presence of MEA

in patients with ZES and in their familyReceived May 1, 1978. membersThis work was supported in part by Grants- „ . , __„

in-Aid from the Ministry of Education, Science H e r e> w e a r e reporting a case of ZESand Culture, the Ministry of Health and Wei- whose diagnosis was strongly suspected byfare, and Development Medical Research examining gastric acid secretion at the timeFoundation for Adult Diseases, Japan. o f first operation, which revealed a tumor

Reprint requests: Kaoru Abe M.D., Endo- , o c a t e d a t f h e f e a s t a i , p o s t t i v e ,crinology Division, National Cancer Center , , • , , , IResearch Institute, 5-1-1 Tsukiji, Chuo-ku, h e w a s a l s 0 exam.ned for the presence ofTokyo 104, Japan. MEA.

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76 TAKAMI et al.Jap. J. Clin. Oncol.June 1978

In the tumor tissue, various polypeptidehormones such as gastrin, calcitonin, vaso-active intestinal polypeptide (VIP), C-pep-tide and insulin were examined either byradioimmunoassays or by immunofluorescenttechniques.

In addition, ZES in Japanese literaturesreported between 1961 and 1976 were re-viewed.

Case Report

A 46-year-old male developed an upperabdominal pain about a year prior to theadmission. The pain had gradually becomesevere especially during the night, and hewas admitted into Yamachika Hospital onFebruary 25, 1976. His family history andpast history revealed nothing particularlyunusual. At the time of admission, he didnot have any abnormal physical findingsexcept for a mild tenderness on the upperabdomen. Neither diarrhea nor fatty stoolwas noticed. Laboratory examinations re-vealed that serum Ca was 9.6 mg%, serumP 2.6 mg%, serum K 4.6 mEq/1, and thefasting blood sugar 160 mg%. Upper G.I.series showed a large niche on the posteriorwall of the duodenum. Examination ofgastric juice disclosed 40 mEq/h of basalacid output (BAO) and 60 mEq/h of maxi-mum acid output (MAO) following 4 /ng/kgof tetragastrin administered intramuscularly.BAO/MAO ratio was 0.67. The diagnosis ofZollinger-Ellison Syndrome was stronglysuspected. The laparotomy was performedon March 5, which revealed an egg-sizedhard tumor located at the pancreas tail. No

metastasis to the regional lymph nodes orthe other organs was noticed. Since duodenalulcer adhered obstinately to the ligament ofhepato-duodenal, an exclusive operation wasperformed. Resection of the antrum asso-ciated with selective vagotomy, gastroente-rostomy by Billroth II method and resectionof the pancreas tail were carried out. Hispostoperative course was uneventful, and hehas completely resumed normal daily life.

1. Hormonal Studies

Before operation:

The plasma gastrin level was 160pg/ml(normal: less than 20pg/ml), which wasreported after the operation.

After operation:

The plasma gastrin levels were determinedin conjunction with calcium and secretin in-fusions based on the method described pre-viously (Abe et al., 1976). As shown inTables 1 and 2, the basal plasma gastrinlevels were within the normal range and didnot increase in response to calcium or se-cretin infusions.

2. Studies on Multiple Endocrine Adeno-matosis (MEA)

Several endocrine studies were performedpostoperatively to rule out the presence ofMEA. Serum calcium levels were normal inspite of repeated determinations.

Thyrotropin releasing hormone (TRH),500 fxg, was administered intravenously, andthe blood was taken at 0, 15, 30, 60 and120 minutes. The responses of growth hor-

Table 1Calcium Infusion Test

before 10 25 40 55 70(min.)

Gastrin(Pg/ml) 10 10 10

(4.5 mgAg/10 min.)

Table 2Secretin Infusion Test

before 15 30 60 90 120(min.)

gggj 1! 14 .6 18 15 11

(9 CHRU/60 min., Boot's company)

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Vol. 8, No. 1 Z0LL1NGER-ELLIS0N SYNDROME 77

mone (GH), thyrotropin stimulating hor-mone (TSH) and prolactin were examined.Plasma GH and TSH did not show a signifi-cant increase, but plasma prolactin showeda good response (Table 3). Luteinizing hor-mone releasing hormone (LH-RH), 100/ig,plus regular insulin (0.1 U/kg) were ad-ministered intravenously, and the blood wastaken at 0, 15, 30, 60 and 120 minutes. Theresponses of GH, luteinizing hormone (LH)and follicle stimulating hormone (FSH) werealmost normal (Table 4) . Urinary 17-hydro-xycorticosteroids and 17-ketosteroids were6.9 and 7.2 mg/day, respectively.

Plasma T3 and T^ levels were normal. Theplasma human calcitonin level was less than20pg/ml (normal less than 50pg/mI).

3. Pathological and Hormonal Studies onthe Tumor Tissue

The tumor removed from the pancreatictail was solitary, grayish hard, and 5 X 4 cmin size. Histology showed a non-/3 islet cellcarcinoma, which had no definite capsuleand infiltrated into adjacent pancreatic

parenchyma and adipose tissue (Fig. 1).Electronmicroscopic examination of routine-ly formalin-fired specimens revealed endo-crine granules in some tumor cells. Gastrincontaining cells were demonstrated in thetumor tissue by the indirect immunofluo-recent method (Fig. 2) . The immunofluo-rescent method also demonstrated insulin ina small number of tumor cells.

The tumor tissue was extracted by theboiling water (Yanaihara et ah, 1977). Thelyophylized powder was dissolved in 0.01 Mphosphate buffer and assayed with three ormore dilutions to obtain a dose responsecurve. The contents of hormones such asgastrin, C-peptide (C-P), vasoactive in-testinal polypeptide (VIP) and calcitoninwere studied by using respective radioim-munoassays.

As shown in Table 5, immunoreactivegastrin was found to be present in amountsof 40,000 ng/g wet weight. ImmunoreactiveVIP and calcitonin were also found to bepresent in the tumor extract at amounts of2.4 and 84 ng/g wet weight, respectively,

GH (ng/ml)TSH (tU/ml)Prolactin

(ng/ml)

Table 3TRH Test

before 15

1.1 4.73.0 5.0

8.7 23

30

4.35.1

20

60

3.94.7

13

120(min.)

2.03.1

7.4

Table 4lOO^g LH-RH plus Regular

LH (ng/ml)FSH (ng/ml)GH (ng/ml)

before

48180

5.0

15

120210

9.3

30

120270

9

Insulin Test

60 120(min.)

94 78240 250

.3 3.7 1.4

(0.1 unitAg)

Table 5Hormone Concentration in the Tumor Tissue

Gastrin C-P VIP

Hormone Content 40,000(ng/g. wet. weight)

U.D. 2.4

Calcitonin

84

abbreviations: C-P ^ connecting peptide of the proinsullnVTP ^ vasonctive intestinal polypeptideU.D. •» undetectable

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78 TAKAMI et al.Jap. J. Clin. Oncol.June 1978

Table 6ZES Reported in Japanese Literatures

Chief ComplaintNo. Age Sex (on initial

operation)

t Gastricft.0* Juiceu l c c r (mEq/h)

GastrinLevel

(pg/ml)

Course afterJ L ! l the InitialOperation operation

1 39 M upper abdominal duodenum hyperaciditypain

2 69 M hematemesis stomach hyperacidityconstipation

3 43 M upper abdominal stomach hyperaciditypain, hemate-mesis

4 43 M upper abdominal stomach hyperaciditypain

gastric resec-tion withpancreas tailresection ofulcergastricresection,B-I

gastricresection

stomal ulcer

stomal ulcer

5 38 F (+) hyperacidity

6 51 M upper abdominal duodenum, hyperaciditypain, melena stomach

gastricresection

stomal ulcer

7 35 M abdominal tumor stomach, hyperacidity& watery diarrhea duodenum

laparotomy abdominalpain, ileus

45 M duodenum, hyperaciditystomach

9 57 M epigastralgia stomach hyperacidity

10 65 M upper abdominal duodenum,pain, melena, stomachhematemesis

11 55 M upper abdominal duodenum hyperaciditypain, melenahematemesis

12 57 F pancreatic tumor stomach at night2000ml/12hfree acid164mEq/l

13 72 M watery diarrhea, stomach hyperacidityhematemesis,melena

gastricresection

gastricresectionwith B-Ugastricresection

stomal

stomal

ulcer

ulcer

laparotomy stomal ulcer

no operation

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Vol. 8, No. 1 ZOLLINGER-ELLISON SYNDROME 79

FinalOperation

total gastrec-tomy with pan-creatic body &tail resectiontotal gastrec-tomy with pan-creas head andtail resectionsubtotalgastrectomyresection ofpancreatic headsubtotal gas-trectomy andvagotomy withtumorresection

total gastrec-tomy resectionof tumorpancreatoduo-denectomy

gastric resec-tion

Number j ^ e t a .

ation

1 (-)

1 (+)

4 (-)

4 (-)

5 (-)

3 lymphnodes onpan-creas

1 (-)

4 (-)

4 (-)

1 (-)

4 (-)

1 liver

0 ( - )

Tumor

Location

pancreastail

pancreas

pancreasbody

pancreastail

pancreashead

duodenum

pancreasheadmultiple

pancreastail

pancreashead

pancreasbody andtailpancreas

pancreas,multiple

pancreaticbody

Pathology

non-y? isletcell adenoma

islet-cellcarcinomanon-/3 isletcell adenoma

islet cellmicro-adenomatosis

islet celladenoma

non-/? isletcellcarcinoma

non-fi isletcell adenoma

non-)3 isletcell adenoma

islet cellmicro-adenomatosisislet cellmicro-adenomatosisislet cellhyperplasia

islet cellcarcinoma

pancreasduct cellcarcinoma

Outcome

alive

died

alive

died

died7 days pop. (pneu-monia)

died ofileus 11days p op.

alive

alive

died10 days pop.

alive

died ofhemate-mesis &melena

Remarks

MEA?serum Ca11.4 mg%serum. K1.9-3.3mEq/lG T T -DM pattern

ulcer inseveralmembers offamilyIt.-adrenaltumor

Reporter(year)

Murata (1961)

Kozawa(1963)Daikoku etal. (1964)

Murata et al.(1965)

Yaoreported byTanaka(1966)Yoshinaga(1966)

Oda (1966)

Murata et al.(1967)

Murata et al.(1967)

JHamaguchi &Komi( 1967)

Abe et al.(1967)

Sugisakiet al.(1967)

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80

No.

14

15

16

17

18

19

20

21

Age

57

65

33

13

64

53

33

28

Sex

F

M

F

M

M

M

M

F

Chief Complaint(on initialoperation)

epigastralgia

upper abdominalpain

epigastralgia

epigastralgia,melena

pyloric stenosis,upper abdominalpain

upper abdominalpain

upper abdominalDain. vomitine.

TAKAMI et al.

Location ofInitial UlceT

stomach

duodenum

duodenum

duodenum

stomach

duodenum

stomach,duodenum

duodenum

Gastric GastrinJuice Level

(mEq/h) (pg/ml)

hyperacidityat night950ml/12hhyperacidity

hypersecre-tion

*2MAO 11.5

hyperacidity #32550(N=<100)

MAO 24.6ratio 0.79

Jap.June

InitialOperation

subtotalgastrectomyB-Igastric resec-tion, B-I

gastricresection

gastricresection

gastricresection

gastricresectionB-I

gastricresectionB-ngastricresection

/. Clin. Oncol.1978

Course afterthe InitialOperation

stomal ulcer

stomal ulcerwaterydiarrheastomal ulcer

stomal ulcerupperabdominalpain

stomal ulcerhematemesis

stomal ulcerhematemesis

22 40 M hematemesis

23 25 M

25 56

duodenum # 2BAO 45.4MAO 60.3ratio 0.75

BAO 33.6MAO 59.5ratio 0.56

pain

F attack ofhypoglycemia

$2390-860

#3180-640

24 44 M upper abdominal stomach, BAO 10.5 265

26 37 M

duodenum MAO 28.1ratio 0.59at night1100ml/12hrs

duodenum,stomach

(+) hyperacidity

gastricresectionB-U

gastricresectionB-U

upperabdominalpain,hematemesisupperabdominalpain,hematemesis,melena

resection of Co^-irradia-pancreatic tion to thetail & spleen liver

27 40

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Vol. 8, No. 1 ZOLLINGER-ELLISON SYNDROME 81

Final dumber M e ( a .Operation ° \ ^ r ' stasis

Tumor

Location PathologyOutcome Remarks Reporter

(year)

1

subtotal gas-trectomy withduodenaltumor resection

gastric resec-tion, R-Y

gastric resec-tion

gastric resec-tion & vago-tomy, resectionof pancreatictailtotal gastrec-tomy

total gastrec-tomy, resectionof transversecolon

totalgastrectomy

gastricresection R-Y

pancreasbody & tail

duodenum

pancreas,multiple

pancreas

pancreastail

pancreastail

pancreas

pancreastail

islet cellmicroadeno-matosissubmucosaltumor

islet celladenoma

islet cellcarcinoma

non-3 isletcellcarcinomanon-/f isletcarcinoma

normal onmacroscopicobservationislet cellhyperplasia

alive

alive

died ofbleeding 14days p op.died

died ofbleeding

died ofcancer in2.5 yearsP op.

alive

died on 22days p op.

alive

alive

alive

Murata et al.(1967)

Yamaguchi &Hiramatsu(1968)

Kishimoto etal. (1968)

Hirota et al.(1968)

MEA? Nagai(1968)

Hisama et al.(1969)

Tanaka & Tai(1972)

MEA+ Ichinomiya etparathyroid al. (1973)adenomaadrenocorti-cal adenoma

Sugiyama etal. (1973)

Sugiyama etal. (1973)

Segawa et al.(1973)

(angio. andERCP)

subtotalgastrectomyresection ofpancreatictumor

(+) pancreas

( - ) pancreas

( —) pancreas

islet cellcarcinoma

died

diedislet celladenomaislet cell aliveadenoma

Maruyama etal. (1973)

Nagashima etal. (1973)Nagashima etal. (1973)

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82 TAKAMI et al.Jap. J. Clin. Oncol.June 1978

Chief ComplaintNo. Age Ssx (on initial

operation)

GastricJuice

(mEq/h)

GastrinLevel

(Pg/ml)

Initial Course after

<*&• ISJSK28 66 M stomach

29 45 F upper abdominal doudenum hyperaciditypain, hemate-mesis

gastricresection

stomal ulcer,hematemesis,melena

30 37 M upper abdominal duodenum $ 2 $ 2pain 3000- 690-980

5000ml/dayBAO 14.4MAO 22.5ratio 0.64

31 44 M G.I. symptoms stomach hyperacidity elevated

gastricresectionB-U

gastricresectionB-II

upperabdominalpain, tarrystool, stomalulcer

hematemesisdiarrhea

33 38 M

34 46 M

35 44

36 57 M

37 42

38 58

39 40

perforation

thoracic pain,hematemesis,melena

upper abdominalpain

hematemesismelena

upper abdominaland back pain

duodenalperforation

duodenalperforation

stomach

duodenum

cardiaduodenum

duodenum

duodenum

duodenum

hyperacidity2000-2500 ml/24hrs

hyperacidityratio 0.65at night1750ml/12h

BAO 19.28MAO 7.09ratio 2.72

hyperacidity

BAO 35MAO 56.3ratio 0.62at night2100ml/12hhyperacidityratio 0.14

hyperacidityratio 0.5

hyperacidity

preoperation1400-1800postopera-tion normal

preoperation1400,postopera-tion200-normal

1300

after #2 op.1M 4253M 1630

18M 65523M 557#2630, 1380

gastricresectionB-n

subtotalgastrectomyresection ofthe pancrea-tic body &tailgastricresectionB-I

gastricresectionB-IIlaparotomybiopsy

gastricresection,B-n

gastricresection

gastricresection

perforation,melena

stomal ulcer

stomal ulcer

stomal ulcer,upper ab-dominal pain

hematemesisand melena

stomal ulcer

stomal ulcerhematemesismelena

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Vol. 8, No. 1 ZOLLINGER-ELLISON SYNDROME 83

Final dumber M e t a .Operation VtiAn stasis

Tumor

ation Location PathologyReporter

(year)

totalgastrectomyresection ofpancreatic tailgastricre-resection

vagotomy

totalgastrectomyresection ofpancreatic tail

0 pancreas

pancreas

pancreas

pancreas

pancreaticbody

islet cell died ofhyperplasia cerebral

bleedingislet cell died ofcarcinoma cancer

micro- diedadenomatosis

2 adenoma &micro-adenomatosis

non-3 isletcell adenoma

normal onmcarcoscopicobservation

died

alive

alive

MEA?

waterydiarrhea

MEA-1pituitaryhyperplasiaparathyroidhyperplasia

MEAparathyroidmicro-adenomaadrenalmicro-adenoma

antral G cellhyperplasia

Emoto (1973)

Hirate andNegishi(1973)

Sugiyama etal. (1973)

Yamada et al.(1973)

Yoshizaki etal. (1973)

M. Abe(1974)

totalgastrectomy,R-Y

selective vago-tomy resectionof tumor

( - )

totalgastrectomy,partial pan-creatomy andsplenectomyresection ofpancreatic tail

totalgastrectomy

2

2

1

2

3

3

( - )

liver

lymph-nodeliver

liver

( - )

pancreatichead

pancreas

pancreastail

pancreastail

pancreaticbody

non-/? isletcell adenoma

malignantislet celltumor

non-/? isletcellcarcinoma

non-/? isletcellcarcinomaislet celladenoma

alive

alive

alive

alive

died

Ca. andSecretin testbeforeoperation

#3Ca. & Sec.test

Endo, A.,et al. (1975)

Emina &Yura (1975)

Shiono et al(1975)

Endo, I., etal. (1975)

Inomata et al(1975)

Tomita et al(1975)

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No. Age SexChief Complaint

(on initialoperation)

GastricJuice

(mEq/h)

GastrinLevel

(Pg/ml)

InitialOperation

Course afterthe InitialOperation

40 59 M stomachduodenum

41

42

43

44

37

42

68

34

M

M

M

M

upper abdominalpain

upper abdominalpain

upper abdominalpain

perforationbleeding

duodenum

duodenum

stomach

duodenumstomach

hyperacidity

#2BAO 4.1MAO 3.5

#2BAO 40

82BAO 4.6MAO 5.3ratio 0.86

#2920tumor4820pg/mg*284(normal<20)

#2145-180(normal <20)

gastricresection,B-ngastricresection

gastricresection

gastricresection

stomal ulcerupper ab-dominal painstomal ulcer

diarrheastomal ulcer

45 71 upper abdominalpain

stomach #550(normal<20)

gastricresection

stomal ulcerhematemesismelena

46 32 F upper abdominal duodenum hyperacidity p op.pain ratio 0.76 26M 405

42M 970

47 66 F vomitting duodenum hyperacidity 1300-3200

48 46 M upper abdominal duodenum BAO 40 792pain MAO 60

ratio 0.67

gastricresection,B-n totalvagotomygastricresection

antrum re-section, B-IIselectivevogotomy

stomal ulcer

vomittingupper ab-dominal painno problem

# indicates the number of operation, and the studies were performed prior to this operation

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Vol. 8, No. 1 ZOLLING ER-ELLISON SYNDROME 85

Final "umber Meta-Operation o t

a ^ r " stasisTumor

Location PathologyOutcome Remarks Reporter

(year)

pancreas non-5 isletcellcarcinoma,immuno-staininggastrin ( + )

Miyoshi et al.(1976)

subtotal gastrec-tomy resection ofpancreatic tailtotalgastrectomypartial resec-tion of pancreastotalgastrectomypartial resec-tion of pancreas

totalgastrectomyresection ofpancreatictumor

totalgastrectomypartiat resec-tion of pancreas

totalgastrectomy

subtotalgastrectomy

( - )

4

3

2

3

5

4

2

1

( —)

( - )

( —)

( - )

( - )

( + )liver

(+)liver

( - )

pancreatictail

pancreas

pancreasmultiple

pancreas

pancreas

pancreas

gallbladder

pancreastail

islet cellhyperplasia

4 non-/?islet celladenomas

non-5 isletcell adenoma

non-/? isletcell adenomaimmuno-staininggastrin ( + )

non-5 isletcell adenomaimmuno-staininggastrin ( + )

non-5 isletcellcarcinoma

non islet cellcarcinomaimmuno-staininggastrin (+ )tumor tissuegastrin39.6//g/g

alive

alive

died

alive

died

alive

died

alive

#2Ca test(positive)

#2Ca test(positive)MEA-Ifamilyhistory ( + )MEA-1familyhistory ( + )PTHl.Ong/ml(normal 0.3)GH (acro-megalicresponse toglucose &TRH)before #5 opCa & Sec test(positive)MEA ( + )thyroidadenoma,GI tractcarcinoid,adrenaladenoma,

Ca & insulintest response

Matsuki et al«(1976)

Ando et al.(1976)

K. Abe et al.(1976)

K. Abe et al.(1976)

K. Abe et al.(1976)

Komi et al.(1976)

Hirai et al.(1976)

Takami et al.(1976)

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88 TAKAMI et at.Jap. 1. Clin. Oncol.June 1978

'**&

r-ig. I : Histology oi non-/-: islet eel! carcinoma showing infiltration to the sur-rounding tissue without definite capsule. (H.E. X650)

Fig. 2: The presence of gastrin in the cells of the islet cell carcinoma, revealedby indirect immunofluorescent method, using rabbit antiserum to synthetic gastrin(supplied by Dr. N. Yanaihara, Shizuoka College of Pharmacy, Shizuoka).(X400)

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Vol. 8, No. 1 ZOLLINGER-ELLISON SYNDROME 87

Table 7Pathological Findings of ZES Reported

in Japanese Literature

Cases examinedAdenoma (multiple)Carcinoma (meta +)Microadenomatosis

or hyperplasia

No. of

401615

9

Case

( 6)(11)

or hyperplasia was found to be present innine cases.

In Table 8, surgical procedures reportedin this series were summarized with theiroutcome. The patients received total gastrect-omy as a final surgical procedure had abetter result than those who received partialgastrectomy alone, suggesting that total gast-rectomy was a choice of treatment for ZES.

but C-P was undetectable.

A Review of Japanese Literature

Forty-eight cases of ZES reported in theJapanese literatures between 1961 and 1976were reviewed in Table 6. Most of thesecases were collected through Japanese CentraRevuo Medicina (Igaku Chuo Zasshi). In 40of the 48 cases, tumor or hyperplasia wasidentified surgically or pathologically, andthe other eight cases were diagnosed byclinical features associated with elevatedplasma gastrin levels. Of the 40 cases, 39were of a pancreatic origin, and one had anon-/? islet cell carcinoma of the duodenum.

Pathological observations examined in 40cases were summarized in Table 7. Sixteencases had adenoma, and six cases of the16 had multiple adenomata. Fifteen caseswere carcinoma, and metastases were pres-ent in 11 of the 15 cases. Microadenomatosis

Discussion

Though a report of plasma gastrin wasnot obtained prior to the operation, thegastic acid studies indicated the presence ofgastrinoma. Therefore, the pancreas was ex-amined carefully, and a tumor found at thepancreas tail was removed with resection ofthe antrum combined with selective vagot-omy. These operative procedures were suc-cessful in this case. The clinical symptomssubsided, and plasma gastrin levels returnedto normal and did not respond to eithercalcium or secretin infusion.

As shown in pathological review of ZESin Japanese literatures, six cases of the 16adenomas had multiple adenomata and ninecases had microadenomatosis or hyperplasia.In addition, 11 cases of the 15 carcinomaswere found to have metastases. These resultsindicated that resection of the gastrinomawas not always a choice of treatment. Wilson(1973) recommended that total gastrectomywas the best surgical procedure to treat ZES

Table 8Surgical Procedures Reported in Japanese

Literature and their Outcome

Cases Alive Rate ofOutcome

Without gastrectomyPartial gastrectomyPartial gastrectomy plussubsequent total gastrectomyTotal gastrectomy at the beginning

720

141

110

10

50%

71%100%

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88 TAKAMI et al.Jap. J. Clin. Oncol.June 1978

from the studies of their registered cases,and our data supported his conclusion.

As for this case, total gastrectomy wasnot performed, and there is a possibility ofrecurrence in the future. Therefore, weare following him carefully. In general, cal-cium and secretin infusion tests are the mostsensitive and reliable method to detect therecurrence of the gastrinoma.

It is interesting to note that this tumortissue was proved to contain immunoreac-tive calcitonin and VIP in addition to largeamounts of gastrin. The immunofluorescencestudy demonstrated the presence of tumorcells contained insulin. These data suggestthat this was a case of multiple hormoneproducing tumor and that large amounts ofgastrin which was produced in the tumortissue evoked the clinical features in thiscase.

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