Proceedings of the 26th annual meeting Chiba, Japan, October 18–20, 1984

GastroenterologiaJaponica Vol. 20, No. 4 Copyright �9 1985 by The Japanese Society of Gastroenterology Printed in Japan

P R O C E E D I N G S OF T H E 2 6 T H A N N U A L M E E T I N G

Chiba , J a p a n , October 18-20, 1984

Chai rman: Kunio OKUDA, M.D., Ph.D.

I n v i t e d lectures:

Liver and pancreas transplant up-date

Shunzaburo JWATSUKI

Dept Surg, Univ o f Pittsburgh Sch Med, Pittsburgh, USA

Since the first clinical liver transplantation on March 1, 1963 by Dr. T. E. Starzl at Denver, Colo- rado, 424 patients with various liver diseases have

received orthotopic liver transplantation before July 31, 1984 at University Health Sciences Center of Colorado and University Health Center of Pitts-

burgh. Before March, 1981, 170 patients were treated

with "conventional triple drug therapy", which con-

sisted of azathioprine (or cyclophosphamide), pred-

nisone and antilymphocyte globulin (ALG). 35 % of these 170 patients survived 1 year, and 18% survived

5 years. Only 2 patients died after 5 years and the longest survivor is doing quite well after 15 years.

Since the introduction of new immunosuppression therapy with cyclosporine and low dose steroid in March, 1981, 254 patients have received orthotopic liver transplantation. Since then 1 year survival rate has risen to 70%, and 5 year survival rate of 50% is expected.

The history of pancreatic transplantation is as long as that of liver transplantation. Yet, for less than 50 % of the pancreas grafts, either segmented or islet cells, still function after 1 year. Many of the failures are contributed to surgical technical prob-

lems. Although experience in Pittsburgh is limited in numbers, with our refined surgical technique of

total pancreas-duodenum-spleen transplant 6 out of

7 pancreas grafts are functioning as of July, 1984.

Gastrointestinal abnormalities in immunodeficiency

Paul E. HERMANS Mayo Clin, Rochester, USA

Gastrointestinal abnormalities have been recognized in a mumber of immune deficiencies. Can- didiasis of unusual chronicity that may imvolve the nails, skin, and mucosa of the oral cavity, the esophagus and lower intestinal tract afflicts patients with T-cell deficiencies. Conditions in which Candidiasis may be prominent include congenital severe combined immunodeficiency (SCID), the DiGeorge syn-

drome (thymic hypoplasia with hypoparathy-

roidism), the Nezelof-Allibone syndrome (thymic hypoplasia), chronic mucocutaneous Candidiasis

(CMC), and the acquired immunodeficiency syndrome (AIDA). Some patients with T-cell lympho-

mas, leukemias, and patients who received organ transplantation may develop mucocutaneous candidiasis. Additional, although poorly defined, gastrointestinal problems are severe diarrhea and malabsorption in SCID, diarrhea in the Wiskott-Ald- rich syndrome, selective vitamin B12 malabsorption in Ataxia telangiectasia, malabsorption and entero- colitis in the Nezelof-Allibone syndrome.

In chronic mucocutaneous candidiasis pernicious anemia, malabsorption, chronic hepatitis and cirrhosis, and cholelithiasis at young age have been de- scribed.

Gastrointestinal abnormalities have been studied in more detail in common variable immunodefici-

ency (CVID) also known as late onset idiopathic

hypogammaglobulinemia, because CVID is the most common idiopathic immunodeficiency in man and patients usually live with the deficiency for many years. In a series of 50 patients with CVID

which we have studied we have found achlorhydria (44%), pernicious anemia (19%), cholelithiasis

August 1985 Proceedings of 26th Annual Meeting 381

(32%), and gastrointestinal neoplasia (14%). The

neoplastic lesions included carcinoma of the sto-

mach in 4 patients, carcinoma of the sigmoid in 1,

lymphoma of the rectum and cecum in 1, polyposis

of the colon in 1 patient. Diarrhea occurs in 60% of

patients with CVID and malabsorption in 61% of

patients with diarrhea. The malabsorption may be

extremely severe and a more serious threat than the

pyogenic infections these patients suffer from. In

64% of the patients giardiasis is implicated. Other

causes include cryptosporidiosis and bacterial over-

growth. The small bowel abnormalities observed in

CVID consist of blunting of villi, mucosal atrophy

and lymphocytic infiltration of the submucosa with

or without nodular lymphoid hyperplasia (NLH).

NLH persists even when malabsorption can be

trated such as in giardiasis. The biopsy findings

(small bowel, rectum) in a recent patient with CVID

and cytomegalovirus infection are ulcerations and

cytomegalovirus inclusion cells.

One of the most severe immune deficiencies dis-

covered in recent years is acquired immunodefici-

ency syndrome (AIDS). AIDS occurs in several high

risk groups, especially male homosexuals and re-

cipients of contaminated blood or blood products.

The deficiency affects mainly the subset of helper T-

cells that vanishes as the disease progresses. A multi-

tude of severe and persistent or recurrent infections

leads to death in a few years in most patients with

AIDS. In a few patients a cryptosporidium species

has recently been implicated in the persistent severe

diarrhea. Morphologic evidence will be demon-

strated showing the first instance in which crypto-

sporidium also caused an ascending cholangitis.

Hepatocellular carcinoma and HBV vaccine

R. Palmer BEASLEY

Univ o f Washington Med Res Unit, Taipei, Taiwan

Hepatocellular carcinoma (HCC) is one of the

commonest cancers in the world and chronic HBV

virus infection is the usual underlying event preceed-

ing its occurrence. Throughout the world most cases

occur among persons with serological markers of

HBV infection, most of whom are HBsAg carriers;

only a small proportion show no evidence of prior

HBV infection. Even though there is striking world-

wide geographic variation in the incidence of HCC,

there is a close international correlation with the

prevalence of HBsAg carriers. In a prospective study

of 22,707 middle age men in Taiwan, a relative risk

of HCC incidence among carriers and non carriers is

200, and the estimated life-time risk of death from

HCC and /o r cirrhosis is approximately 40 %.

Many HBV carriers in the world were probably

infected in early life by their own carrier mothers,

those carriers resulted from perinatal infection may

be the source of infection for other children. Mother

to child transmission appears to have unique impor-

tance in relation to HCC.

Hepatitis B vaccine derived from plasma has been

shown safe and immunogenic to newborns. Studies

demonstrated more than 90% protection efficacy

against perinatal infection by given both HBIG and

vaccine, and approximately 75% efficacy if only

vaccine to the newborns. Breaking mother-to-child

transmission will break most secondary routes of

transmission. The number of carriers can be re-

duced by 90%, and the incidence of HCC can also

be dramatically reduced, by control of perinatal

transmission with HBIG and vaccine, at least in

Asia.

Hepat i t is B virus and related viruses

of animals

Jesse SUMMERS

Fox Chase Cancer Inst, Philadelphia, USA

Hepatitis B is the result of infection of liver cells

by a virus with interesting and unusual biological

properties. This virus apparently does not cause

cytopathic injury by itself, but persists in the cells,

causing the cells to produce large amounts of viral

specific proteins and infectious virus. Host immune

responses against viral specific antigens on the sur-

face of the infected hepatocytes are thought to be re-

sponsible for the recurrent hepatocellular injury

seen in chronic active hepatitis B. Thus, interrup-

tion of the ability of persistently infected cells to pro-

duce viral antigens is necessary to prevent progres-

sion of the disease. We have studied the molecular

382 Proceedings of26th Annual Meeting Vol. 20, No. 4

events in the replication cycle of the hepatitis B virus

(HBV) in order to understand how viral production

might be interrupted.

In order to investigate this process we identified

two HBV-like viruses that infect animals that can be

used in experimental studies. The woodchuck he-

patitis virus (WHV) and the duck hepatitis B virus

(DHBV) are closely related phylogenetically to HBV

yet infect only their respective hosts. Using liver

from DHBV-infected ducks, we have identified the

major steps in the viral replication cycle. Surprising-

ly, we found that HBV-like viruses closely resemble

retroviruses in their replication strategy. Retro-

viruses comprise a large and diverse group of viruses

that are similar in their biological properties to

hepatitis B virus. Retroviruses are highly oncogenic

in animals, and a recent isolate has been shown to

cause a T-cell derived leukemia in man.

Since hepatitis B virus infections are oncogenic in

man, it is possible that some mechanisms of onco-

genesis studied in retroviruses may apply to HBV in-

fections in man. The woodchuck hepatitis virus

causes hepatocellular carcinoma in a high propor-

tion of infected woodchucks, and we have investi-

gated possible mechanisms for hepatocarcinogenesis

using this model system. No clear mechanism has

emerged from these studies.

Subacute hepatic failure

B.N. T A N D O N

Dept Gastroenterol, All Med Sci, New Delhi, India

Subacute hepatic failure characterized by persist-

ence of jaundice and development of ascites 4 weeks

after the appearance of icterus in patients with acute

hepatitis has been found to be a common manifesta-

tion of viral hepatitis in India. A collaborative study

at 3 major referral centres in the country registered

90 such patients in a period of 18 months which in-

cluded 62 males and 28 females. 5 major clinical

features included-- jaundice, ascites, pedal edema,

hepatomegaly and splenomegaly. Abnormalit ies of

liver function were non-specific. Virus B and virus

non-A non-B were etiological agents for 48.6 and

48%, respectively. Virus A was the cause in 3.4 per

cent. Glucagon therapy did not help the prognosis.

Mortality rate was 68%. Histopathology of the liver

showed acute viral hepatitis with bridging necrosis.

LMI index was negative in high proportion, but pri-

mary effector T-cells were not decreased. Associated

infection with non-A non-B in hepatitis B antigen

positive was suggested in 2 out of 15 patients.

S y m p o s i u m (1):

Approaches to early detection of hepatocellular carcinoma Modera to r s : H i rosh i O B A T A a n d Ryuj i M I Z U M O T O

Super high risk group of hepatocellular carcinoma

Kenichi KOBAYASHI* and Yoshio KINAMI**

*1st Dept Intern Med, Sch Med **2nd Dept Surg, Kanazawa Univ

In order to detect early HCC, what cases with cir-

rhosis might belong to the super high risk group was

investigated. Clinical material comprizes 32 resected

and 69 non-resected cases with HCC of which the

size of the main tumor was below 5 cm in diameter.

27 of 32 resected cases were radically operated and

the remaining 5 cases had multiple lesions. Capsule

formation was observed in 19 of 32 cases (59%). In-

filtration beyond capsule was found out in 9 of 24

cases (38%) of which the size of the main tumor was

above 2 cm in diameter and in 2 of 8 cases (25%) of

which the size of the main tumor was below 2 cm in

diameter. On the other hand, capsule formation was

suspected in 15 of 41 non-resected cases (37%) by

US examination prospectively. The survival t ime of

28 resected cases with cirrhosis was 79% one year

after the operation and 64% two years and 50%

three years according to the life time table method.

August 1985 Proceedings of 26th ,4nnual Meeting 383

On the contrary, the survival t ime of 69 non-

resected cases was 48%, 28% and 0%, respectively.

11 of 28 resected cases with cirrhosis were the follow-

up cases. The risk score tha t we h a d proposed was

above 6 points in 10 of 11 cases. Serum HBsAg was

positive in 8 of 11 cases. The m e a n period from the

diagnosis of cirrhosis to the association of HCC was

2.4 years. 30 of 69 non-resected cases were the fol-

low-up cases. 16 of 30 cases (53%) had had the risk

score above 6 points at the diagnosis of cirrhosis.

From these results, it is suggested tha t the super h igh

risk group is put stress on the follow-up intervals and

methodologies by using US and so on for detect ing

early HCC.

Pa tho log ic study on growth pattern

of smal l l iver cancer

Masamichi KOJIRO and Toshiro NAKASHIMA

1st Dept PathoI, Kurume Univ Sch Med

In order to clarify the pa tholomorphologic char-

acteristics, part icular ly tumor growth pat tern , of

small liver cancer (SLC), we have studied 27 cases of

hepatocel lu lar ca rc inoma up to 2 cm in d iameter

among 472 autopsy cases of hepatocel lu lar carcino-

ma. Among the 27 cases, SLC was solitary in 14

cases and was mult iple (2-3 nodules) in 13 cases.

Extracapsular tumor growth: 24 of the 27 cases of

SLC were encapsulated. Varying degrees of extra-

capsular tumor growth was found in 6 of the 14 cases

of solitary SLC and 7 of the 13 cases of mult iple one.

All the tumors growing over the capsule showed a re-

p lacing growth pa t te rn , in which the tumor cells

prol i ferated as if they were replacing the hepatocytes

along the liver cell cords.

T u m o r th rombus of the por ta l vein: T u m o r

th rombus of the porta l vein was found in 4 of the 14

cases of solitary SLC and in 8 of the 13 mult iple one.

Overall incidence of tumor th rombus of the porta l

vein was 44 .4% in SLC.

In 10 of the 13 cases of mul t ip le SLC, tumor

nodules were located closely each other and most of

them were in terpre ted as in t rahepa t ic metastases via

porta l vein in the early stage.

Possibility of so-called " la tent carc inoma": Liver

cirrhosis was associated in 77.7 % of SLC. In 3 cases,

associated cirrhosis was highly a t rophic and the

tumors were encapsula ted by thick fibrous capsule

without forming an extracapsular invasion and

tumor th rombus of the portal vein. All of them died

of hepat ic failure or rup tu re of esophageal varices.

It was presumed tha t SLC occurr ing in highly

a t rophic cirrhosis migh t not grow fast and some of

them might be considered so-called " la tent carcino-

m a" ra ther t han early cancer.

A his topatho log ica l s tudy of 34 resected

cases of smal l l iver cancer less than 3 cm in diameter

Akihiro TOYOSAKA and Eizo O K A M O T O

1st Dept Surg, Hyogo Coil Med

Materials and Methods: 160 cases of hepatocellu-

lar carc inoma (HCC) were resected at this clinic in

the past 11 years. Of them 34 (21.3%) were small

liver cancers less t han 3 cm in diameter . For these 34

patients, the survival was good with 1-year survival

ra te being 86% and 3-year survival rate 73% com-

pa red with pat ients with HCC more t h a n 3 cm in

diameter .

Result: The his topathological study on these

small HCC showed in t racapsu la r invasion in most

cases, extracapsular invasion in 70%, vascular inva-

sion mainly in the pa renchym a round the capsule in

50% and in t rahepat ic metastasis in 44%. In 10 pa-

tients with tumor less t han 2 cm in diameter , how-

ever, the rates of vascular invasion and in t rahepat ic

metastasis were bo th only 20%. In the macroscopic

classification, of the 34 cases, 28 (82.4 %) were of the

nodu la r type with a capsule and 6 (17.6%) of the

small massive type wi thout a capsule. The small

massive type shows a low rate of in t rahepat ic meta-

stasis and good prognosis with all of the 6 pat ients

surviving and their average survival t ime being 2

years and 3 months . In the Edmondson 's classifica-

t ion, the small HCC consisted pr imari ly of differen-

t ia ted cells mainly of Ed. I and II types, while only

the Ed. I type was found in 4 cases. In the AFP value

the small HCC consisting only of Ed. I and II types

showed low values, while the those conta in ing Ed.

III type showed high AFP level in many cases. The

possibility of the vascular invasion and in t rahepat ic


metastasis was high in patients with levels 1000

n g / m l or more.

Summary: A considerable advance was already

seen even the small liver cancer, and it appears

necessary to detect smaller nodules of 2 cm or less.

References: 1) Okamoto E, et al: Results of surgi-

cal treatment of primary hepatocellular carcinoma:

some aspects to improve long term survival. World J

Surg 8: 360-366, 1984.2) Okamoto E, Toyosaka A,

et al: The significance of hepatic lobectomy as the

surgical treatment for primary hepatocellular car-

cinoma. J J p n Surg Soc 84: 912, 1983.3) Okuda K,

Nakashima T: Hepatocellular carcinoma: A review

of the recent studies and development. Schaffiner,

editors. New York, Grune & Stratton, 1979, pp

639-650

Clinicopathological studies of minute hepatoma and diagnosis of tumor

growth by various imaging modali t ies

Shunsaku HIGASHI and Ryuji MIZUMOTO

1st Dept Surg, Mie Univ Sch Med

Of 62 resected cases with hepatocellular carcino-

ma for the past 8 years in our clinic, 23 (37.1%) had

a minute hepatoma with the tumor of less than 3 cm

in diameter, including 19 cases (30.6%) with the

tumor of 2 to 3 cm and 4 cases (6.5%) with the so-

called 'small liver cancer ' of less than 2 cm. 22

(95.7 %) of the 23 cases with a minute hepatoma had

liver cirrhosis. 17 (87.5%) of the 19 tumors of 2 to 3

cm and only one (25%) of 4 small liver cancers had

capsule. Capsule invasion was observed in 64.7 % of

tumors of 2 to 3 cm and even in the only one case of

small liver cancer with capsule. Tumor emboli in

the portal system and daughter nodules were ob-

served in 36.8% and 21.1% in the tumors of 2 to 3

cm, respectively. In small liver cancer, neither

tumor emboli in the portal system nor daughter

nodules were observed. 75% of small liver cancer

grew up with replaced type in an intimate correla-

tion with their adjacent portal veins. Therefore, it is

considered that in an early stage, hepatocellular

carcinoma grows up with replaced type and there-

after forms capsule in cirrhotic liver, but it still

shows replaced type of growth in noncirrhotic liver

even when it has grown to a large size, resulting in

high frequency of tumor emboli in the portal system

and daughter nodules. The absolute values of serum

AFP was not useful on diagnosis of small liver can-

cer, but the rapid elevation was useful on it. Among

various imaging modalities, US was the most useful

to diagnose a small liver cancer, However, none of

these modalties were effective to evaluate a tumor

growth.

The diagnosis of the capsule, capsular invasion, and vascular invasion of

the small sized hepatocellular hepatomas

Yoshinori ISOBE and Akiko SAITOH

Inst Gastroenterol, Tokyo Women's Med Coll

Improvement of the diagnostic equipments has

made the detectability of the small sized hepatomas

up to 2 cm in diameter higher and given further de-

tailed information about the morphological status

of the tumors. So far HCC with fibrous capsule has

been remarked on its prognostic aspect. 50 nodules

of HCC less than 5 cm in diameter in 48 cases, which

were confirmed pathologically by the operation,

were evaluated for the capsule, capsular invasion

and invasion into the portal vein. All of 48 cases had

ultrasonic and angiographic examination. 37 cases

were done CT. Of 50 nodules, the so-called small

liver cancer up to 2 cm in diameter were 13. The

diameter of the smallest solitary nodule is 1.1 x 1.2

cm. Of 13 small liver cancers, 9 had the fibrous cap-

sule macroscopically. US was able to make diagnosis

for the existence of 49 nodules (98%). This result

suggests that US may be the most useful modality for

screening of HCC. On the diagnosis for ttie existence

of the capsule, the angiography showed relatively

high diagnostic accuracy rate (83.3 %). The findings

of the capsule were; 1, well demarcation of the

tumor nodule, 2. halo on US, ring-like enhance-

ment on CT, lucent r im on angiography. On CT

and angiography, the diagnostic accuracy tended to

depend on the thickness of the capsule. Concerning

to the extracapsular invasion of the tumor, US was

most reliable for its diagnosis (78.8%). But it

August 198.5 Proceedings of 26th Annual Meeting 385

seemed to be quite difficult to diagnose the extracapsular invasion in the small liver cancer.

(0-33%). The similar result was given in the diagnosis for the invasion into the portal vein. Even in the small liver cancer, three had the invasion to the peripheral portal rams, but it appeared to be miserable

to make it diagnosis. The appearance of A-P shunt on the angiography was relatively reliable finding suggesting the portal vein invasion. In addition to these modalities, the angio CT and/or lipiodol CT

could give the further detail, so it should be better to perform the angio CT, if available.

Comparative diagnosis of small hepatocellular carcinoma and daughter

nodules by various imaging techniques

Shoichi OHUE and Hajime OHISHI Dept Radiol, Nara Med Univ

The detectability was investigated for 46 hepatocellular carcinomas smaller than 3 cm in diameter by US, CT and angiography and for daughter nodule in 117 bepatocellular carcinomas by CT after intrahepatic arterial infusion of Lipiodol (LpCT) and infusion hepatic angiography (IHA). In small hepatocellular carcinomas the detectability by

US and CT amounted to 35.7% and 33.3% respectively for tumors below 2 cm in diameter and to

88.9% and 96.8% respectively for tumors below 3 cm in diameter. Comprehensive diagnosis by a com-

bination of US, CT and angiography identified all the tumors except one case. LpCT demonstrated its excellent diagnostic value in detection of daughter nodules. Small high density areas corresponding to

daughter nodules were visualized in 80 of 117 cases. In 22.5%, they were identified by LpCT alone and in 47.5% LpCT showed a higher detectability of daughter nodules than IHA. In 19.0% daughter nodules were detected in segments other than the area of the main tumor. Compared to IHA that al- lowed only 15.2% detection of daughter nodules of small hepatocellular carcinoma below 3 cm in diameter, the detectability by LpCT amounted to 50%, confirming the higher detectability of

daughter nodules than IHA. This indicates that

LpCT is indispensable for the diagnosis of hepatocellular carcinomas.

Diagnostic procedure for the early stage of hepatocellular carcinoma based on

the study of clinical features and capability of various

diagnostic modalitles

Masaaki EBARA and Masao OHTO 1st Dept Med, Sch Med, Chiba Univ

Seventy-nine patients with hepatocellular carcinoma (HCC), including 34 with tumors smaller than 2 cm in diameter (Group 1), 45 with tumors of 2 to 3 cm (Group 2), were studied according to clinical and pathological findings and the capability of diagnostic imaging modalities. In this study we have at- tempted to define the relationships between tumor size and the early stage of HCC and to make an effective diagnostic procedure for the early stage of

HCC.

In each group there were no characteristic findings in clinical and laboratory data including AFP

of which the level showed normal (less than 20 ng/ml) in 80 percent. Histological findings showed

that there is a difference between these two groups; in Group 1 there was much more invasion of malignant ceils to the extracapsule and portal vein neigh- boring the HCCs than in Group 2. Furthermore, the speed of tumor growth increased when the tumor size exceeded 2 cm in diameter according to the observation of 9 patients who had not undergone anti- cancer therapy. So, it is of great value to detect tumors of less than 2 cm in diameter to make a diagnosis of the early stage of HCCs.

Detectability of various diagnostic modalities for Group 1 HCCs were as follows: 97.1% by ultra-

sound, 25% by plain CT, 37.5% by enhanced CT and 75.9% by angiography.

Ultrasound is the most effective diagnostic modality to detect HCCs and should be performed for patients with chronic liver disease every 3 months.

A limitation of diagnostic imaging modalities in making definite HCC diagnoses exists, especially in its deferentiation from regenerative nodules seen in


liver cirrhosis. Ultrasonically guided biopsy can pro- vide correct diagnosis in 6 out of 7 patients (85.7%) with HCCs in Group 1.

Measurement of reactivity of alpha- fetoprotein with lectins and its

use in the early diagnosis of hepatocellular carcinoma

Yutaka AOYAGI and Fumihiro ICHIDA 3rd Div, Dept Intern Med, Niigata Univ

Sch Med

We have recently observed that measurement of

the reactivity of AFP in serum samples with con-

canavalin A (Con A) and Lens culinaris agglutinin (LCA) is useful for the differentiation of AFP species which are found in association with nonneoplastic

liver diseases, hepatocellular carcinoma and carcinoma metastatic to the liver (Gann, 75, 809-815, 1984). In the present study, we tested the reactivity of AFP with LCA for the purpose of differential diagnosis between benign liver disease and the early stage of hepatocellular carcinoma.

The reactivity of AFP with LCA was studied by crossed immuno-affinoelectrophoresis of the serum samples of 150 patients (101 patients with hepatocellular carcinoma; group I and 49 with benign liver

diseases; group II). In group I, the percentage of LCA-reactive species of AFP was high (44 _ 33, mean _ SD), but the of LCA-reactive species in

group II was very low (3 + 5). A statistically significant difference (p<0.001) was observed between

group I and group II. Furthermore, the percentage of LCA-reactive species of 15 AFP samples of patients with hepatocellular carcinoma, the diameter of which is less than 3 cm, was also higher than that

of patients with benign liver diseases with statistical significance (p<0.005). These results indicate that the measurement of AFP LCA-reactive species is useful for the detection of minute hepatocellular

carcinoma.

Laser and ultrasonic laparoscopy in the diagnosis of hepatocellular

carcinoma

Kenichi IDO and Ken KIMURA

Dept Gastroenterol, Jichi Med Sch

1, Diagnosis of hepatocellular carcinoma by

cancer fluorescence excited by argon laser. A fluorescence was recognized identicallly in the

area of hepatocellular carcinoma when the lesion was exposed to an argon laser light. This phenome-

non was observed not only on the resected specimen

of the liver, but also laparoscopically on the liver surface with hepatoma in both human patients and rats. The fluorescence was, however, sometimes observed also on the adipose and fiberous tissues of the liver.

Then, an administration of HpD and/or the apectrum analysis of the fluorescence are considered necessary for the further specific diagnosis of hepatocellular carcinoma.

2. Diagnostic usefulness of ultrasonic laparoscope.

A newly developed flexible ultrasonic laparoscope incorporates a oblique viewing fiberscope for accu- rate orientation. A linear electronic real-time scanner of 50 MHz is contained in the top of the

laparoscope. In the clinical use, the scope was well

manipulated without much trouble. From the results obtained from the clinical use of

these three procedures of ordinary laparoscopy, con-

vertional ultrasonography and the present ultrasonic laparoscopy in 20 patients with hepatocellular carcinoma, it is definitely concluded that the ultrasonic laparoscopy showed the best diagnostic ability in the detection of the small cancer especially located deep inside the liver.



D i a g n o s i s and treatment os p r i m a r y b i l i a r y cancers

M o d e r a t o r s : I tsuo M I Y A Z A K I a n d H a r u o K A M E D A

An early diagnosis of ca rc inoma of the

gal lb ladder and ext rahepat ic bile

ducts by ul t rasonography

Yukihiro TSUCHIYA and Masatosi SUMIDA

1st Dept Med, Chiba Univ

We investigated the possibility of diagnosing an

early stage carcinoma of the biliary tract by means

of ultrasound.

Carcinoma of the gallbladder: Out of the 21 pa-

tients with an early carcinoma, 17 (81%) had a

polypoid type on macroscopic findings, while the re-

maining 4 (19%) had an infiltrative type or a flat

type. And, there was a close relationship between

the tumor size and the grade of infiltration of car-

cinoma into the wall of the gallbladder; the poly-

poid tumor less than 20 m m in size had no sub-

serosal infiltration. These suggest that there is the

possibility to detect by ultrasound in most of early

carcinomas of the gallbladder. The result of clinical

survey by abdominal ultrasound examination indi-

cated that 2.4% (175/7371) had a small polypoid

lesion. Almost all could be diagnosed as cholesterol

polyps by ultrasound, but it had limitations in

differential diagnosis for those of about 10 mm in

size.

Carcinoma of the bile ducts: There was a close re-

lationship between the presence or absence of jaun-

dice in patients with bile duct carcinoma and the

grade of its pathological extent; most of the patients

without jaundice (5/6) had an early carcinoma

(Grade I or II), while more than half of those with

jaundice (20/31) had an advanced stage (III or IV).

This data suggests that to detect an earlier carcino-

ma the patients should be screened before occur-

rence of jaundice. Since 1978, we detected 4 cases of

bile duct carcinoma without jaundice in our depart-

ment.

Conclusion: Ultrasound is a very useful modality

for screening carcinoma of the biliary tract of an

early stage.

Different ia l diagnosis of p ro tuberan t

lesions of the gallbladder by PTCCS and P T D C C

Kazuo ICHIKAWA and Saburo NAKAZAWA

2nd Dept Intern Med, Nagoya Univ Sch Med

We reported results of percutaneous transhepatic

cholecystoscopy (PTCCS) developed by us and per-

cutaneous transhepatic double contrast cholecysto-

graphy (PTDCC) using bar ium and CO~ while

studying the diagnostic capability of of the conven-

tional methods and results of ultrasonically-guided

gallbladder puncture cytology. The usefulness of

PTCS for cancer of the bile duct was also men-

tioned.

Results obtained were as follows.

1. There was a limit to the qualitative diagnosis

for protuberant lesions of the gallbladder by the

conventional image-guided diagnostic methods.

2. There was a limit to the suction/puncture

cytology at the site of tumor for cancer in the rela-

tively early stage.

3. PTCCS and PTDCC not only permitted ob-

servations on minute changes in the mucous mem-

brane but also were capable of making a histologic

diagnosis by biopsy under direct vision. PTCCS

proved to be the most excellent test method for the

qualitative diagnosis of protuberant lesions of the

gallbladder, particularly for the diagnosis of cancer

of the gallbladder in the early stage.

4. PTCS was capable of making an established

diagnosis of cancer of the bile duct and diagnosis of

the advance of cancer in the mucosa lateral to the

liver as well as diagnosis of the advance of cancer in

the lateral wall of the liver to some extent.

Operabi l i ty of b i l la ry t ract mal ignancies

by computed tomography

Kimiyoshi MIZUNUMA and Shimpei T A D A

Dept Radiol, Sch Med, Jikei Univ

388 Proceedings of26thAnnualMeeting Vol. 20, No. 4

We studied the efficacy of computed tomography

(CT) for operability of biliary tract malignancies.

Thir ty three gallbladder cancer cases and 31 bile

duct cancer cases were examined CT and the macro-

scopical findings confirmed by laparotomy (55 cases

including 22 resected cases) and autopsy (9 cases).

CT findings of gallbladder cancer were devided into

three CT patterns. Resected case numbar in each

CT patterns; 7/22 cases in massive type, 1/10 case in

wall thickening type & 0/1 case in intraluminal

type. In 8 resected cases, massive type occupied

seven cases. In 22 cases having mass lesion in hepato-

duodenal ligament, 20 cases were unresectable.

Hepatic extension of bile duct cancer was seen as

surrounding low density area of bile duct on CT.

Macroscopical finding of this low density area

agreed with Hinf3 in 3 non-resected cases. In 29 bile

duct cancers excluding intercurrent death, 13 cases

had hepatic extension CT finding or invasion to por-

tal vein like as mass formation with cancer and por-

tal vein. In these 13 cases, 12 cases were not re-

sected. The remaining one case was resected,

though invasion to hepatic artery was present. In 16

bile duct cancer cases without hepatic extension CT

findings or invasion to portal vein like as mass

formation with cancer and portal vein, 15 cases were

resected. The remaining one case had bile duct infil-

tration and not resected.

CT is very useful study for evaluating operative in-

dication of biliary tract malignancies.

C om bined use of ul t rasonical ly-guided

punc tu re cholecystography and bile

cytology in the diagnosis of

bi l ia ry system c a r c i n o m a

Nobuo BOTO and Makoto MIYAJI

1st Dept Intern Med, Med Sch, Nagoya City Univ

Ultrasonically-guided puncture cholecystography

was performed in 116 cases with negative cholecysto-

grams by IVC, ERCP and PTC. The puncture

cholecystograms were classified into 4 types accord-

ing to the form of the neck of the gallbladder or the

end of cystic duct. Type II which showed a "Schat-

tendefekt" or irregular margin were all gallbladder

carcinoma and most of biliary duct carcinoma re-

vealed Type III which showed a U or V shaped ob-

struction. The differentiall diagnosis of gallbladder

carcinoma and biliary duct carcinoma which

showed obstructive jaundice by cytology of the gall-

bladder bile and biliary duct bile was impossible

when both cytology were positive or negative, while

possible when either cytology was positive. Com-

bined use of cholecystography and both cytology of

the bile made a differential diagnosis of gallbladder

carcinoma and biliary duct carcinoma possible in 11

of 17 cases. It is, therefore, considered that these

methods should be used together.

Cl inico-pathologlcal study of tumorous

lesions of the ga l lb ladder and sig-

nif icance of selective percutaneous

t ranshepat ic cholecystography

in the patients of early

ga l lb ladder cancer

Eiichi ASANO and Takukazu N A G A K A W A

Surg 2, Sch Med, Kanazawa Univ

We clinically reviewed tumorous lesions of the

gallbladder and investigated the metaplasia and

dysplasia of tumor-surrounding mucosa. We further

reported significance of selective percutaneous

transhepatic cholecystography (SPTC) in the pa-

tients of these lesions.

The material consisted of 37 gallbladders with

tumorous lesions. These are divided into 8 malig-

nant tumors (polypoid type early gallbladder can-

cer, 5 m, 3 pm) and 29 benign tumorous lesions (2

adenoma, 3 metaplastic polyps, 9 inflammatory

polyps, 8 adenomyoma, 7 cholesterol polyps).

The gross and microscopic findings of the lesions,

as well as the age, sex, and symptomatology of the

patients in each division are reported and discussed.

Malignant tumors ranged in size above 0.5 cm in

diameter and were sessible. Regarding the metaplas-

tic epithelium and dysplasia of tumor-surrounding

mucosa in 8 resected polypoid typed early gallblad-

der cancer, the incidence rate of goblet cell typed

metaplasia was 87.5%, and that of dysplasia was

100%. Based on the results of the metaplastic

changes and dysplasia obsereved in the mucosa sur-


rounding the polypoid typed early gallbladder cancer, microscopic findings in benign tumorous lesions were investigated. The results indicate that adenoma, metaplastic polyp, and inflammatory polyp possess the malignant potentiality.

Since 1975, we have performed 180 cases of SPTC to diagnose the early gallbladder cancer. The results indicate that cytology and bile juice CEA value are significant of malignant tumors. And, endoscopic

biopsy by SPTC is proposed to diagnose these benign lesions.

Early carcinoma of the gallbladder:

Diagnosis and surgical implications

Joji ISEKI* and Tomoe BEPPU** *Dept Surg, Shizuoka Gen Hosp * *2nd Dept Surg, Univ of Tokyo

Fifteen cases of early carcinoma of the gallbladder, confined to the mucosal and muscular layer,

were analyzed clinicopathologically. Forty cases of polypoid lesion, ten cases of severe dysplasia, and eight cases of carcinoma with minimum subserosal involvement of the gallbladder were compared with carcinomas in early stage. In two patients the superficial flat type carcinoma was found postoperatively by histological examination of the gallbladders removed for presumed benign disease. In four patients the superficial elevated type carcinoma was dis- covered intraoperatively by careful observation of the resected gallbladders. Macroscopically, this type

carcinoma showed a raised mucosal plaque or multiple tiny projections. The severe dysplasia,

adenoma, adenomyoma, or inflammatory granula- tion of the gallbladder sometimes showed a resem- bling appearance to the superficial elevated type

carcinoma. In five among nine patients of protruded type carcinoma, gallstones were not present, and the tumor could be detected preoperatively by ultra-

sonography or cholangiography. In the remaining four patients associated with gallstones, the preoperative diagnosis was not established. Involvement of lymph nodes was not seen in the cases of early carcinoma. The prognosis in these early carcinomas was good. On the other hand three among eight patients of carcinoma with subserosal involvement had

lymph node metastases, and three patients died of recurrent carcinoma within two years. It was ex-

tremely difficult to evaluate the extent of mural invasion of gallbladder carcinoma during operation. This fact led to the conclusion that extended chole- cystectomy with regional lymph node dissection should be principally performed for carcinoma in grossly early stage.

Minute excrescences of the gallbladder: A comparative pathological study for

their differential diagnosis

Hiromichi SATO andJishu ITO Dept Pathol, Kawasaki Hosp, Kawasaki

Med Sch

For the earlier detection of smaller gallbladder cancers, a comparative morphological study was made between 14 intramucosal carcinomas and 65 minute excrescent lesions of various kinds from the gallbladder. The intramucosal carcinomas were of solitary occurrence, classified either as polypoid type (8 cases) or bosselated type (6 cases), the former ranging 0.2 to 2.5 cm (average 1.1 cm) in diameter and being stalked in 4, while the latter, 1 to 4 cm (average 2.2 cm) and sessile in all, comprising irre-

gular conglomerates of minute papillary to nodular

lesions. The minute excrescent lesions included 29 hyperplastic polyps (so-called sessile adenoma)l), 22

cholesterol polyps, 6 adenomas, 4 inflammatory and 2 lymphoid polyps. The hyperplastic polyp was smaller than 6 mm in diameter, sessile and smooth- surfaced. The cholesterol polyp was smaller than 7 mm in diameter, stalked and lobular-surfaced. The adenoma was smaller than 6 mm in diameter, stalked and smooth to papillary-surfaced. The inflammatory polyp was smaller than 5 mm in diameter, stalked and papillary-surfaced. The lymphoid polyp was smaller than 3 mm in diameter, sessile and smooth-surfaced. Multiple occurrence was positive in 13/29 cases of the hyperplastic polyp, 9/22 cases of the cholesterol polyp, 1/6 case of the adenoma, 2/4 cases of the inflammatory polyp and 2/2

cases of the lymphoid polyp. Each of these minute excrescences in the gallblad-

der indicated characteristic features in the size, sur-

390 Proceedings of26th .4nnualMeeting Vol. 20, No. 4

face appearance, three-dimensional structure and

multiplicity, the combination of which may contri-

bute to their differential diagnosis in endoscopic or

imaging examination.

Reference: 1) Sato H, et al: Sessile adenoma of

the gallbladder: Reappraisal of its significance as a

precancerous lesion. Arch Path Lab Med: in press

Surgical t rea tment of h i l a r carcinoma of the bi le duct

Yoshifumi OGURA and Ryuji MIZUMOTO


Of malignant tumor in the biliary system, car-

cinoma in the hepatic hilum is the most difficult to

manage surgically, since many of these tumors can

not be resected curatively and even a palliative bili-

ary decompression can not be easily performed.

In this paper, surgical t reatment of carcinoma in

the hepatic hilum and its results in our clinic were

presented.

Out of the 30 cases with carcinoma in the hepatic

hilum who underwent surgery in our clinic for the

past 8 years, 27 cases (90.0%) had resection, but

curative resections could be performed only in 12

cases (40.0%).

Hepatectomies were carried out in 15 cases, in-

cluding 13 cases of major hepatic resections, such as

trisegmentectomy in 5 and lobectomy in 8, and 2

cases of hilar hepatic resection.

Out of these 15 hepatectomy cases, 9 cases had the

combined resection of the caudate lobe, including 8

cases (88.9%) with the curative resection. 12 cases

underwent resection of extrahepatic bile duct alone

without hepatectomy, including only one case

(8.3 %) with the curative resection.

The cumulative postoperative survival rate was

analyzed according to the operative procedures. In

the 15 cases with hepatectomy, one-year survival

rate was 76.6% and the survival rate of 2 to 5 years

were all 35%. On the other hand, in 12 cases with

resection of the extrahepatic bile duct alone, one-

year survival rate was 36.7%, and none was alive

longer than 2 years after surgery. All 3 cases without

resection died within one year after surgery.

As a result, every effort should be made to remove

hilar carcinoma, as complete as possible, especially

emphasizing an usefulness of an extended hepatec-

tomy according with resection of the caudate lobe as

curative operative procedures.

Reevaluat ion of the operat ive procedure for carcinoma of the gallbladder

Hidehiro KAWAGUCHI and Terukazu M U T O

1st Dept Surg, Niigata Univ Sch Med

We reevaluated the operative procedure for car-

c inoma of the gallbladder prospectively.

Materials and Methods: Over of fifteen-year and

nine-month period, 89 patients with carcinoma of

the gallbladder were operated upon. In thirty eight

of the 89 patients (42.7 %) tumor was resected, and

in twenty six patients (29.2 %) curative resection was

performed. By the Kaplan-Meier method, three-

year survival rate of 38 patients with resection was

42.1% and fively-year survival rate 31.6%, and

three-year survival rate of 26 patients with curative

resection was 60.4%, five-year survival rate 45.3%.

In twenty two patients with tumor localized in the

w~/ll of the gallbladder, three- and ten-year survival

rates were 63.0% and 43.2% respectively. In con-

tradistinction to these patients, three-year survival

rate in patients whose tumor spreaded into or arised

from the cystic duct was low (16.7%). All of the fac-

tors including perineural invasion, lymphnode

metastasis and invasion into the hepatoduodenal

ligament, contributed to the low survival rate in

these patients. Conclusion (1) For the patients with

localized carcinoma in the gallbladder enbloc chole-

cystectomy with wedge resection of the gallbladder

bed dissection of the lymphatic bearing tissue of the

hepatoduodenal l igament and posterior superior

pancreato-duodenal nodes was considered to be the

procedure of choice. (2) For the patients whose

tumor spreaded into or arised from the cystic duct

pancreato-duodenectomy and wide lymphnode dis-

section should be performed. (3) We recommend to

fix immediately the removed gallbladder in 10%

formalin solution for ten minutes, because it is use-

ful to confirm the extent of carcinoma of the gall-

bladder at operation.


The rationale of the surgical treatment for carcinoma of the bile ducts

and gallbladder

Toshiharu TSUZUKI and Yoshiro O G A T A

Dept Surg, Keio Univ Sch Med

From January 1971 to September 1984, 86 pa-

tients with carcinoma of the bile ducts and 53 pa-

tients with carcinoma of the gallbladder were ad-

mit ted to Keio University Hospital.

For the 46 patients with carcinoma of the proxi-

mal bile ducts, extensive resection of the bile ducts

combined with a hepatic lobectomy was a standard

operation with resectability rate of 45.6 per cent.

For the 40 patients with carcinoma of the distal bile

ducts, pancreaticoduodenectomy was the procedure

of choice with resectability rate of 90.2 per cent.

Cancer of the gallbladder tended to spread exten-

sively to the surrounding organs with peritoneal dis-

semination. Twenty one patients underwent resec-

tion of various types with resectability rate of 39.6

per cent.

The surgical treatment for carcinoma of the bile

ducts and gallbladder is now focused to increase re-

sectability rate and long-term survival.

Reference: 1) Tsuzuki T, et al: Carcinoma of the

bifurcation of the hepatic ducts. Arch Surg 118:

1147-1151, 1983

Endoscopic biliary drainage for the inoperable bile duct carcinoma

Mikiko ONO and Satoru SOHMA

1st Dept Surg, Kyorin Univ Sch Mecl

In the terminal stage of the bile duct carcinoma,

patients suffered from severe obstructive jaundice

and died of that in most cases. Endoscopic biliary

drainage (EBD), which was developed by Soehendra

in 1979, is excellent method for the reduction of the

jaundice insuring the quality of their remaining lives.

The procedure of EBD: First of all, informations

of whole biliary system should be obtained by echo-

gram and PTC. At the beginning of EBD, endo-

scopic sphincteropapillotomy is performed so that

the drainage tube could not block the pancreatic

orifice. After an ERCP cannula is put into the bile

duct, a guide wire inserted through this cannula is

push upwards beyond the obstruction, and the can-

nula is removed. An EBD tube covering the guide

wire is pushed by a pusher tube untill it's tip has

reached to the upper part of the obstruction and re-

mained there being an internal fistula between the

bile duct and the duodenum.

The clinical results: We have performed this

method in 7 cases of malignant jaundice for 2 years.

4 of 7 cases --2 cases of papillary carcinoma, 1 case

of carcinoma of the gallbladder and 1 case of meta-

static liver carcinoma from the stomach -- seemed to

be well drained and serum bilirubin level got down

to normal within 12 days. The remaining 3 cases --2

of carcinoma of the gallbladder and 1 of pan-

c r e a s - died from pneumonia, DIC and advanced

carcinoma shortly after this method and seemed to

be drained ineffectively. The main causes of the in-

operability were the distant metastasis and demen-

tia.

From these results, we can say that EBD is easier

to at tempt in the cases of which obstructions are

short and extra-hepatic than multiple and /o r intra-

hepatic. As a conclusion, we emphasize that EBD is

the best way for the patients in their terminal stage

reliefing from any tubes on their body and insuring

rather comfortable lives though it has technical

difficulties in some cases.

392 Proceedings of26th AnnuaI Meeting Vol. 20, No. 4

Sy mpo s i um (3):

Diagnosis , treatment and prognosis of smal l pancreat ic cancer

Modera to r s : Ryo ich i T S U C H I Y A a n d M u n e a k i A B E

How to make diagnosis of small pancreatic cancer and points upon treatment

Yasuhiro H A R A and Hideyasu KIYONARI

Natl Hosp, Kyushu Cancer Cent

We have already reported in 1977 that obstructive

pancreatitis induced upon compression of pancre-

atic duct by tumor could be a useful clue to make

the diagnosis of small pancreatic cancer.

Among 8 pancreatectomied cases in our experi-

ences due to cancer on the body of pancreas, eleva-

tion of serum amylase was noted on those with

tumor sizes ranging from Ta to Ts, but those with

tumor larger than that did not show any increase of

amylase. Accordingly, it is important upon diagno-

sis of small pancreatic cancer to get hold of obstruc-

tive pancreatitis at the initial stage. In case of car-

cinoma on the head of pancreas, which used to be

thicker and broader than that on the body, symp-

toms are more complicated due to the presence of

main pancreatic duct, accessory pancreatic duct

and common bile duct, therefore, under sufficient

considerations on these anatomic positions the diag-

nosis should have to be made.

Next, as to t reatment of pancreatic cancer, even if

it is resected, a very poor prognosis is expected, ac-

cording to the reports and the speaker's experiences.

At the present stage, surgical resection only is not

considered to be sufficient, therefore, intraoperative

and postoperative irradiations are used to be ap-

plied to those not resectable looking forward to ob-

taining effective results, as well as multiple chemo-

therapy centered on 5-Fu and MMC should posi-

tively be applied to the postoperative cases.

Early detection of pancreatic cancer by elevated serum pancreatic

enzymes

Tetsuo H A Y A K A W A and Naoyuki K A T A D A

2nd Dept Intern Med, Nagoya Univ Sch Med

Attempts to detect cancer of the exocrine pan-

creas at an early stage by measuring serum factors

have been evaluated by a retrospective study of 40

pancreatic cancer patients (PCA) and a prospective

study of 722 GI patients over 40 years old for 2 years.

Among the 40 patients incidence of elevated values

were 30% by serum amylase (SA), 70% by immuno-

reactive elastase (IRE), 28% by CEA and 68% by

CA19-9. The highest incidence were 89% by IRE

(CA19-9 59%) in 27 patients with head cancer, and

85% by CA19-9 in 13 patients with body-tail cancer.

Eighty-three percent of patients underwent radical

resection showed high IRE values (45 % in unresect-

able cases) and 77% of patients with unresectable

tumor demonstrated high CA19-9 (56% in resect-

able cases). Combined assays of IRE and CA19-9

would be useful for detection of PCA from an early

to late stages. IRE was determined prospectively in

722 GI patients over 40 and having either of the fol-

lowing symptoms; epigastric pain or discomfort,

weight loss, diabetes, jaundice, or palpable mass.

Among the 722 patients, high IRE was found in

23%, including 77% of 22 patients with PCA, 69%

of 29 patients with chronic pancreatitis and 100 % of

14 with acute pancreatitis. Radical resection of PCA

could be done on 10 of 17 patients with high IRE.

Early detection of pancreatic cancer should be ap-

proached by measuring IRE instead of an imaging

technique in selected patients with high risk factors.

Clinical study of 14 cases of small pancreatic cancer under 2 cm

in tumor size

Tadashi MIYASHITA and Takashi SUZUKI

1st Dept Surg, Kyoto Univ Sch Med

Since 1965, 14 cases of pancreatic cancer smaller

than 2 cm in size were experienced and treated by

macroscopically curative resection in our clinic.

Main symptoms on admission were jaundice in 9

cases and abdominal pain or other in 5. In all the


cases, tumors were located in the pancreat ic head

and made invasion or compression on the common

bile duct or on the ma in pancrea t ic duct. As pre-

operat ive diagnostic tools, combina t ion of cho-

langiography and pancrea tography picked up

lesions in all the cases. Recent in t roduct ion of CT

and US yielded some advantages in visualization of

the tumor itself in several cases and of di lated com-

m o n bile duct or ma in pancrea t ic duct in all the

cases. CA19-9, a not iceable t umor marker , was

evaluated in 7 cases of this series, but only in one

case CA19-9 level was over cut off level (37 U). In

order to detect small pancrea t ic cancer before mani-

festation of jaundice, elevation of pancreat ic enzyme

is an impor tan t diagnostic clue. In this series, elas-

tase 1 showed abnorma l elevation in a higher ra te

than serum or ur ine amylase.

Of these 14 cases, while dis tant metastasis, liver

metastasis and peri toneal implants were not present,

macroscopic infi l trat ion to the anter ior surface of

the pancreas was observed in 3 cases, re t roper i toneal

invasion in 3, por ta l invasion in 3 and microscopic

lymphnode metastases in 6.

Among 14 pat ients of this series, five are current ly

alive, bu t not beyond 3 years after surgery. One died

of DIC induced by chemotherapy 2.0 months after

operat ion. One died of apoplexy after 24.9 months

and ano ther died of liver abscess after 4.5 years post-

operatively. The remain ing 6 pat ients died of recur-

rence of the disease within 2 years after operat ion.

Improvement of operat ive result is still a pend ing

problem.

Diagnosis , surg ica l t r e a t m e n t a n d prognosis

of smal l p a n c r e a t i c cance r

Yoshiro O G A T A and Shoichi HISHINUMA

Dept Surg, Keio Univ Sch Med

After January 1971, 9 cases of small pancrea t ic

cance r (TI) which m a x i m u m d iamete r is less than 2

cm after fixation in formalin , were t reated at Keio

University Hospital. In all cases tumors were located

in the head of the pancreas. All 9 cases were resect-

able and occupied 13.6% in 66 resectable cancer of

the head of the pancreas.

Ini t ial symptoms were obstructive jaundice in 6

cases and epigastralgia in 3 cases. All cases except

one showed obstructive jaundice at admission.

Among diagnostic methods, super selective angio-

graphy showed most correctly the size of tumor .

POA was positive in last three examined cases, bu t

ano ther tumor markers CA19-9 and CEA were

negative.

Seven cases were t reated with pancrea t icoduo-

denectomy and 2 cases were with total pancreatec-

tomy. Combined resection of portal vein was re-

quired in 5 cases. Even in small pancrea t ic cancer,

por ta l vein and d u o d e n u m were invaded according

to its location and lymphnode metastasis were shown

in Ns.

Prognosis is be t te r than larger size of pancrea t ic

cancer. Now three cases are living wi thout sign of re-

currence at 56, 52 and 13 months after surgery.

A c lue of de tec t ion of resectable smal l

c a r c i n o m a of the pancreas

Eii KARASAWA* and Hiromitsu SAISHO**

*Dept Intern Med, Yokohama-higashi Natl Hosp

* *1st Dept Intern Med, Chiba Univ Sch Med

We have 12 cases of resected small ca rc inoma of

the head of the pancreas which are 2 cm or less in

size. Hal f of them had upper abdomina l symptoms

such as epigastric pain, r ight hypochondr ic pain and

loss of appeti te three months on the average before

jaundice developed. Positive rates of fast ing blood

sugar, serum amylase, elastase 1 and O - G T T ac-

counted for 30%, 50%, 75% and 70%, respective-

ly. Diagnostic accuracies of ul t rasonography, com-

pu ted tomography, endoscopic re t rograde pan-

crea tography and selective angiography were 89%,

14%, 57% and 33%, respectively.

In three out of four cases without jaundice a mass

was able to be del ineated by ul t rasonography, bu t in

the remainder one, the diagnosis was made by endo-

scopic re t rograde pancrea tography .

Elastase 1 was considered to be useful for detect-

ing pancreat i t is secondary to obstruct ion of the pan-

creatic duct by small carc inoma.

Ul t rasonography was superior to o ther imaging

modali t ies in detect ing small ca rc inoma of the pan-


creas.

Cl inical eva lua t ion of small resectable pancreatic carcinoma

Masafumi SUYAMA andJo ARIYAMA

Dept Gastroenterol, Juntendo Univ

During the past 12 years, 140 pancreatic carcino-

mas have been studied. Thir ty tumors (21%) were

resected and the smallest lesion measured 1.0 x 0.9

era. Seventeen tumors were less than 2 crn and 12 of

them were resected (70%). Mean survival t ime of

patients with resected small tumor was 23 months

while in those with unresectable tumor mean sur-

vival time was 5 months. Ultrasonography and com-

puted tomography failed to detect small pancreatic

carcinoma. However, in some patients dilatation of

the pancreatic duct was delineated. ERCP was the

most sensitive examinat ion in the detection of small

tumor. In all patients obstruction or stenosis of the

pancreatic duct system was present. Angiography

was useful to differentiate chronic pancreatitis from

pancreatic carcinoma, and to predict resectability.

Conclusion: 1) Where small pancreatic carcino-

ma is resected survival of the patient will be im- proved.

2) Ultrasonography is best suited for the screen-

ing of pancreatic carcinoma. ERCP is the most sen-

sitive in the detection of small tumor. Angiography

establishes the diagnosis and predicts accurately re-

sectability.

Clinical evaluation of endoscopic ultrasonography (EUS) in diagnosis

of small pancreatic cancer

Sotaro FUJIMOTO and Masatsugu NAKAJIMA

Dept Gastroenterol, Kyoto 2nd Red Cross Hosp

In the diagnosis of small pancreatic cancer, the

conventional morphological diagnostics (ex. ERCP,

US, CT and Angiography) have limits of these

ability. From April 1980, we have used 4 types of

ultrasonic endoscope with secta scan transducer

(Olympus Optical Co. Ltd.), and examined 16 cases

of pancreatic cancer (3 cases under 20 mm in size, 1

case between 20 to 30 m m and 12 cases over 30 ram)

and 3 cases of focal pancreatitis.

These cancerous lesions of pancreas were clearly

shown as a low echo mass in all cases, and the focal

pancreatitis had a tendency to show uniformal and

sharp marginal echo mass. Each size of the lesions

measured by EUS corresponded well to the resected

specimens. The positive finding rate of EUS was

100%, and each rate of ERCP, US, CT and Angio-

graphy was 81%, 50%, 75% and 83%. Compared

with conventional diagnostics, EUS was the most

useful method for detection of small pancreatic can-

cer. However, the strict differential diagnosis be-

tween the focal pancreatitis and the pancreatic can-

cer was difficult.

References: 1) Yasuda K, et al: Use of endoscopic

ultrasonography in small pancreatic cancer. Scand J

Gastroenterol 19 (suppl 102): 9-17, 1984. 2)

Fujimoto S, et al: Endoscopic differential diagnosis

between pancreatitis and pancreatic cancer. Tan-

to-Sui 5: 975-982, 1984

Report on small pancreati cancer

Toshimitsu MIYAMOTO and Ryoichi TSUCHIYA

2nd Dept Surg, Nagasaki Univ Sch Med

In the period between September 1969 and

December 1983, 146 cases of carcinoma of the pan-

creas were presented in our department, 26 of which

were resectable excluding 2 cases of cystadenocar-

cinoma and 1 ease of islet cell carcinoma. There

were 59 cases of carcinoma of the pancreatic head

(19 cases were resectable), 47 cases of the body and

tail (7 cases were resectable), and 40 cases of entire

pancreatic cancer among which none were resect-

able.

Moreover, a national survey was carried out con-

cerning so-called small pancreatic cancer (SPCa; T1

cases in which the tumor is less than 2 cm in diame-

ter), and 106 cases including 2 autopsies were pre-

sented. 103 cases or 99% were resectable, and these

included 91 cases of carcinoma of the pancreatic

head, 7 cases of the body, and 5 cases of the tail.

There were 47 cases in Stage I, 43 in Stage II, 12 in

Stage III and 3 in Stage IV.

The following is a description of the resectable

cases in our depar tment (RPCa), and also the cases


of SPCa.

There were 16 cases of RPCa and 53 cases of SPCa

with jaundice, 14 and 31 cases with abdominal pain

and 6 and 14 cases with loss of appetite respectively.

The test that led to diagnosis was PTC in 6 and 40

cases, ERCP in 5 and 28 cases and clinical findings

in 2 and 10 cases respectively. Diagnosis of pancre-

atic cancer using PTC, ERCP and US was 57.7%

for RPCa and 70.8% for SPCa. The resection

method was total pancreatectomy (TP) in l0 and 18

cases, pancreatoduodenectomy (PD) in 10 and 76

cases, and distal pancreatectomy (DP) in 6 and 9

cases respectively.

Follow-up studies of the various stages revealed

that Stage I and /or N ( - ) were naturally better than

the other stages and N(+),

Nowadays the prognosis of resectable cases are

improving, but it is still far from satisfactory when

compared with the carcinoma of other organs. The

diagnosis of early-stage pancreatic cancer must

begin with the diagnosis of SPCa. To that end, it is

very important that blood tests followed by pre-

operative examination by PTC, ERCP and US, be

carried out in patients.

Diagnosis, t rea tment and prognosis of

small ca rc inoma of the pancreas

Eishi MIYASHITA and Seiki MATSUNO

1st Dept Surg, Tohoku Univ Sch Med

From January 1960 to August 1984, ten patients

with small carcinoma (_--<2 cm) of the pancreas were

treated in our Department. Location of carcinoma

was pancreatic head in all patients. Jaundice which

appeared in eight patients was the most important

symptom for diagnostic clue. Correct diagnosis was

achieved by PTC, selective angiography, ERP, US,

CT and cytology of the pancreatic juice. Carcinoma

was resected in nine patients (pancreaticoduodenec-

tomy in seven, total pancreatectomy in two). His-

tologic examination of the operated specimens re-

vealed metastatic lymphnodes in five of nine pa-

tients, cancerous invasion into the lympatic vessels in

three patients, venous invasion in two patients and

pancreatic capsular invasion by the tumor in one pa-

tient. These results were favorable as compared with

the histologic findings which were seen in the opera-

tive specimens from the patients with large car-

cinoma (>2 cm) of the pancreas. However, progno-

sis of the patients with small carcinoma of the pan-

creas was so poor that three-year survival rate was

only 20 percent and no patients survived longer than

four years after operation. Autopsy findings of three

patients with resected small carcinoma of the pan-

creas showed various types of recurrences, viz., local

recurrence, liver metastasis, lymphnode metastasis

and intraperitoneal dissemination.

A histological study on the mode of spread

of the pancreat ic cancer and the

radical i ty of operat ion; with

special reference to

resected T 1 tumors

Yoshiyuki WADA and Akira KURODA

1st Dept Surg, Fac Med, Univ of Tokyo

The patients with duct carcinoma of the pancreas

shows still grave prognosis even after surgical resec-

tion of the tumor. To clarify the point of surgical

t reatment of pancreatic duct carcinoma, we ex-

amined histologically the mode of the cancer spread

in 31 resected specimens (total pancreas: 4, pancreas

head: 23, pancreas body and tail: 4) and analized

the cause of high incidence of cancer recurrence in

these cases.

I) Intrapancreatic spread: Among the 31 speci-

mens, the predominant pattern of tumor growth in

the pancreas was scirrhous in 14, medullary in 4,

intraductal in 3, and a mixture of scirrhous and

intraductal ones in 10. In 5 of scirrhous type and one

of mixed type, the cut ends of the pancreases were

microscopically involved with carcinoma.

II) Extrapancreatic spread: No distant metasta-

sis was confirmed at operation in any case. Most of

the tumors, regardless of the growth patterns,

showed microscopically marked extension outside

the pancreas; directly to the distal common bile duct

in 81%, the duodenum in 29%, and the retropan-

creatic tissues in 84%, with involvement of regional

lymph nodes in 65%.

In 26 out of 31 specimens (84%), infiltrating car-

cinoma was found microscopically just at the dis-

396 Proceedings of 26th Annual Meeting Vol. 20, No. 4

sected margins, mainly within perineural spaces in

the retropancreatic tissues. Even 6 of 10 T1 tumors

(less than 2 cm in diameter on histologic section)

showed the same marginal involvements.

Those results indicated that complete removal of

the direct extension to the retropancreatic tissues by

more wide dissection would be one of the most im-

portant factors for radical operation of, even if

small, pancreatic cancer.

Basic principle of surgical treatment for small pancreatic cancer

Yoshinobu HIGASHINO and

Takukazu N A G A K A W A

Surg II, Sch Med, Kanazawa Univ

Although definition of small pancreatic cancer is

still indefinite, it seems, in general, to be recognized

as tumor less than 2 cm in gross size. Reported re-

sults of surgical t reatment for such cancer, however,

have not been satisfactory. So, this study has been

made to demonstrate the cause of such results and to

discuss the basic principle of surgical treatment.

Twenty nine surgically resected specimens of pan-

creatic head cancer were used for material. Each

specimen was sectioned serially 3 to 5 mm in thick-

ness to examine precise histopathological extension

of cancer. Tumor size histologically determined was

divided into tl (less than 2 cm), t2a (2.1-3.0 cm), t2b

(3.1-4.0 cm), ts (4.1-6.0 cm) and t4 (greater than

6.1 cm). The number of cases was three in tl, 10 in

t2a, 9 in t2b, 6 in ts and 1 in t4. The five year survival

rate except the cases of operative death was 31.2%.

But the tumor size was not always correlated with

prognosis. It was necessary to consider other impor-

tant factors which influenced prognosis; that is, in-

vasion to serosa of pancreas (s factor), retroperito-

neal infiltration beyond pancreas (rp factor) and re-

gional lymph node metastasis (n factor). All patients

with positive s factor died less than 2 years after

operation and the prognosis of those was significant-

ly worse than that of negative patients. S factor was

positive in 33 % of t x, 30 % of t2a and 22 % of t2b. Sur-

vival rate of patients with positive rp factor was 21%

at 2 years and that of negative patients was 75% at 2

years and 50% at 5 years. Rp factor ws positive in

100% of tl, 80% of t2a and 89% of t2b. As for n fac-

tor, prognosis of positive patients was significantly

worse than that of negative patients. These results

suggest that rp factor is most important factor. Fur-

thermore, rp factor is very frequently positive even

in cases of tl and t2a. It is therefore concluded that

extended radical operation by translateral retroperi-

toneal approachX) is basically necessary even for

small pancreatic cancer.

Reference: l ) Nagakawa T, et al: Translateral

retroperitoneal approach in radical surgery for pan-

creatic cancer. J p n J Surg 12: 229-233, 1982

Symposium (4):

Postoperative hepatic damage in cirrhosis Modera to r s : T a k a y o s h i T O B E a n d Yasuyuki O H T A

Pathogenesis and anticipation for the liver injury after transection of esophageal

varix in liver cirrhosis

Akira T A N A K A and Hiroshi SAKAUE

3rd Dept Intern Med, Ehime Univ Sch Med

Transection of esophagus and splenectomy with

supragastric devascularization were performed on

33 cases of liver cirrhotics and 2 cases of idiopathic

portal hypertension accompanied by remarkable

grade of esophagus varix more than F2RC (q+) or

F3RC (+)1) during past 6 years in our hospital.

As grown worse values of liver function tests with-

in 8 weeks after the operation in more than 40% of

cases, worsening of serum bilirubin were observed in

80% of cases, of G O T in 56%, ALP in 49%, choline

esterase (ChE) in 45% and ~-GTP in 45%. The

jaundice as the most prominent feature of post-

August 1985 Proceedings of 26th .4 nnual Meeting 397

operative liver injury reached their peaks of increase

(2.4 -+ 2.6 mg/d l , max 13.6 m g / d l of total bilirubin

in cases of none operative death) on 7th or 14th day

and returned below preoperative levels by 5th week

in most cases. The peak level of bilirubin over 5

mg/d l a n d / o r occurrence of ascites as well as gastro-

intestinal bleeding were followed by continuous

worsening of liver parenchymal cell dysfunction ob-

served as on Kxcc and ChE. Seven cases died within 6 weeks after the opera-

tion accompanied by extream jaundice or ascites

with GI bleeding.

The preoperative value of ChE and KICG, as well

as Child's classification z) were substantiated as the

excellent sign post for the favorable prognosis and

the values of greater than 40 ChE.U. of ChE (nor-

mal range 73-150 ChE.U.) and greater than 0.04 of

KInG were the minimal requirement for uneventful

postoperative course.

References: 1) Inokuchi K: The Jpn j Gastroen-

terol Surg 13: 338-340, 1980.2) Child CG: The liver

and portal hypertension, W.B. Saunders Company,

Philadelphia and London, 1964

Restorative process of human cirrhotic livers following hepatectomy

Naoki YAMANAKA and Eizo O K A M O T O

1st Dept Surg, Hyogo Coll Med

This study reports the restorative processes of the

remaining livers of the cirrhotics (C) after hepatec-

tomy in comparison with those of the non-cirrhotics

(NC). Fifty-four patients entered into the present

study, who had undergone hepatectomies of more

than single segment with primary hepatomas Jan

1979 to Dec 1984. There were 39 who had unevent-

ful postoperative courses, and 15 who had post-

hepatectomy liver failures. In 39 patients compari-

sons of liver functions (Alb, Bil, GOT) and daily in-

creasing rate of the remaining liver during the first

postoperative month (DIR, cmS/day), estimated by

computed tomographyX), were made between NC

(n=13) and C (n=26). These patients were catego-

rized into three classes based on the amount of par-

enchymal hepatic resection rate (RR)2); L:

50%<RR, M: 30~RR--<50%, S: RR<30%.

Means of Alb and Bil completely returned to the

preoperative levels 4 to 5 postoperative mos in C-L,

and 3 to 4 mos in C-M and S. Times of restorations

in C were delayed by 1 to 2 mos compared to NC

among the same classes of RR. Bil and GOT showed

a biphasic elevation in about 60% of both C and

NC. Hepatitis was the cause of the second elevation.

DIR of C-L, 8.0 -+ 1.9 cmS/day (M _+ SE), were

lower than that of NC-L, 18 + 3.0. Liver failures

were separated into two types: (1) acute type with

rapid elevating Bil up to death, (2) chronic type with

persisting moderate hyperbilirubinemia by rapid

elevations due to hepatitis, leading to death. Cirrho-

tic livers functionally could return to the initial

levels with some delay compared to non-cirrhotic

ones. Posthepatectomy hepatitis is a interrupting

factor against the restorative processes.

References: 1) Kanzo 24: 870-877, 1983. 2) Surg

95: 586-591, 1984

Evalua t ion of postoperative hepatic func t iona l reserve

Kazue OZAWA and Shigeki ARII

Dept Surg, Kyoto Univ Med Sch

In order to manage patients competently in the

postoperative management , an effective method to

evaluate the stage of the regenerative process after

cirrhotic liver resection would be of great value.

1. O G T T pattern: Hepatectomized patients

showing a linear G T T pattern for shorter periods

have remarkably greater restorative and regenera-

tive power of the liver after cirrhotic liver resection

than those with longer periods.

2. Blood ketone body ratio: Hepatectomized pa-

tients were classified into 3 groups according to the

postoperative changes in the blood ketone body

ratio: Group A without decrease below 0.7, Group B

with transient decrease to 0.4, and Group C with

progressive decrease to below 0.4. Groups A and B

patients tolerated operation well. All Group C cir-

rhotic patients died of multiple organ failure.

3. Cytochrome A: As far as the contents of cyto-

chrome A of mitochondria from the remaining liver

is from 0.7 to 1.3 x 10-10 moles /mg protein, major

hepatic resection could be performed without corn-


plication and death, patients with marked increase

of cytochrome A contents above 1.5 are less ideal

operative candidates and the percentage of liver re-

section should be less than 30 %.

]sC-aminopyrine breath test as a direct

measurement of hepatic microsomal

funct ion in hepatectomized

patients

Akio S A K A M O T O and Sadahito USUI

2nd Dept Surg, Chiba Univ Sch Med

lsC-aminopyrine breath tests were performed in

13 cases before and after hepatectomy. Five patients

with liver cirrhosis received partial hepatectomy and

8 without cirrhosis got hepatic lobectomy. On the

first day after operation 50 percent decreases of

microsomal function were observed in both group,

however, the recovery rates on 7th day were 100 per-

cent in partially hepatectomized group and 90 per-

cent in another group. It is suggested that small liver

resection will not impair the liver microsomal func-

tion in cirrhotic patients. Cumulative ~sCO2 output

during 2 hours after injection of lsC-aminopyrine

did not decrease below 0.5 percent in partially

hepatectomized patients and 1 percent in the lobec-

tomized group. These values are seemed to be criti-

cal points after hepatectomy with or without liver

cirrhosis.

Preoperative evaluat ion of the funct iona l

reserve of the remnant l iver after hepatectomy, especially from the

view poin t of ICG R m a x

Yoshifumi K A W A R A D A and Ryuji MIZUMOTO


About 80 % of hepatocellular carcinoma are asso-

ciated with liver cirrhosis in our country. In these

cases the functional reserve of the liver and the

reticulo-endothelial system are already impaired be-

fore surgery, and consequently, serious complica-

tions or liver failure may occur after hepatectomy.

During 7 years and 6 months in our clinic, 145

hepatectomies were performed including 50 cases

associated with liver cirrhosis. The postoperative

morbidity and mortali ty were higher in the cirrhotic

patients. Postoperative severe liver dysfunction and

hepatic failure were observed in 15 (30%) out of the

50 hepatectomy cases with cirrhosis. Therefore, it is

important that the operative risk should be evalu-

ated thoroughly before surgery and that the ade-

quate operative procedure should be selected de-

pending on it.

In our clinic, the operative risk was evaluated by

the total risk, measured from the mult ivariant ana-

lyses of the various liver function tests, and the func-

tional reserve of the remnant liver, which was esti-

mated preoperatively by ICG Rmax of the remnant

liver, measured from both the functional volume

rate of the expected remnant liver. Rmax of the unit

liver volume in the remnant liver, which was calcu-

lated from the preoperatively estimated Rmax of the

remnant liver divided by its liver volume measured

on CT, was also used for evaluation on late compli-

cation after hepatectomy.

The prognosis of hepatectomy in early postopera-

tive period may be good, if the preoperatively esti-

mated ICG Rmax of the remnant liver is over 0.4

m g / k g / m i n , and that in late postoperative period

may be excellent, if Rmax of the unit liver volume in

the remnant liver is over 0 . 8 / z g / k g / m i n / c m 3.

Measurement of reserve funct ion of the l iver us ing of hepatic venous blood

flow and ICG clearance

Shuhei I IDA and Toshiharu TSUZUKI

Dept Surg, Sch Med, Keio Univ

From April 1973 to September 1984, 151 patients

underwent hepatic resection at Keio University Hos-

pital.

Fifty-four of the 151 patients were cirrhotic.

Fifteen patients died postoperatively without leaving

hospital. Thir teen of the 15 patients underwent re-

section of more than two segments of the cirrhotic

liver and died of liver failure. Thus to decrease post-

operative motality, it is mandatory to minimize

postoperative liver failure. For this purpose, blood

flow and ICG clearance of the right, middle, and

left hepatic veins were individually measured and

the function of the remaining lobes was calculated.


The patients having a remaining lobe with blood

flow of less than 600 m l / m i n and ICG clearance of

less than 0.1 m g / m i n were prone to succumb to

postoperative liver failure.

Prediction of remnant liver funct ion-- histopathological analysis

J. OKAMURA and M. SAKURAI

2nd Dept Surg, Dept Pathol, Osaka Univ Hosp

Surgical indication in cases of primary liver can-

cers combined with liver cirrhosis can be routinely

determined by some hepatic reserve capacity tests.

They are ICG Rmax, hepaplastin test, O G T T and

so on. Not rarely dissociation between these tests and

postoperative complications and /o r death has been

experienced. In this report, histological findings of

the remnant liver was investigated in an attempt to

elucidate their correlation with tests and prognosis.

Forty-six cases of hepatocellular carcinoma were

analyzed. Intraoperative liver biopsy and postopera-

tive resected liver were used as materials. Liver cir-

rhosis was classified into A, A', B, B' according to

Nagayo a) and Miyake 2's) and subdivided into active

(+, -8-) and inactive ( - ) . Acute exacerbation was de-

fined by the intralobular balooning and spotty

necrosis of the liver cells.

Conclusions: 1) Prognostically, liver cirrhosis

could be classified into 3 groups; inactive, mildly ac-

tive, moderately to severely active.

2) Moderately to severely active cases, when

combined with acute exacerbation, showed the most

worse prognosis.

References: 1) Nagayo M: Liver cirrhosis -- a

study of autopsy material. Tr Soc Pathol Jpn 4:

31-72, 1915 (Jpn). 2) Miyake M: Primary hepatic

cancer and liver cirrhosis in Japan. Tr Soc Pathol

Jpn 49: 589-632, 1960 (Jpn). 3) Mori W: Cirrhosis

and primary cancer of the liver. Cancer 20:

627-631, 1967

Effect of surgery on liver function in liver cirrhosis

Hisao SHIBATA and Shigenori NI l

Dept Intern Med, Kitasato Univ

To evaluate the effect of surgery in liver cirrhosis

on liver function, follow up study was made in 35

cases. Among 35 cases, 7 died within 1 year due to

hepatic failure, and 2 other cases within 5 years. To

know the prognosis after surgery, in 22 cases dis-

criminant analysis was performed. As variables, al-

bumin, gamma globulin and cholinesterase were

used. With this analysis separation of a poor risk

group was possible, although misdiscrimination rate

was 10.2%. Using the linear regression method, the

changing rate of postoperative liver function in each

year was calculated. Comparing the changing rate

in the postoperative and nonoperative group, rapid

deterioration of liver function in the postoperative

group was recognized. Moreover in 14 out of 23

cases receiving surgical t reatment an increase of

ALP over 5 units was formed. From these results,

surgical treatment of esophageal varix in liver cir-

rhosis should be replaced by medical treatment in

the near future.

Post-operative liver damage in

cirrhotic patients

Masahiro SUENAGA, Masumasa HORISAWA

and Tatsuhei KONDO

2nd Dept Surg, Nagoya Univ Sch Med

In order to conduct a study of post-operative liver

damage in cirrhotic patients of the liver, we studied

the changes in liver function and prognosis follow-

ing te rminal esophagopromixa l gastrectomy

(TEPG) for cirrhotic portal hypertension and

hepatectomy of primary liver cancer (hepatoma).

Out of 133 cases of cirrhotic portal hypertension,

3 patients (3.6%) out of the 84 patients who under-

went TEPG died in surgery. In those cases, liver

failure from incomplete suturing was the cause.

Contents of Alb., Bilirubin, KICG, BSP 30 minites,

and other liver function values investigated showed

no significant differences between those in the group

which survived the surgery and those who died.

Death from liver failure within 1 year after surgery

occurred in only one case. In a comparison of the

liver function values Alb., GOT, H P T and KICG

before surgery, the 4th week and 1 year after sur-

gery, other than a drop in the KICG value in the 4th


week after surgery, there were no significant differ-

ences from the values before surgery.

In hepatectomy of primary liver cancer, of 53

cases, 10 patients died during surgery, 3 of them

from complete liver failure, but 2 due to massive

hemorrhage during the surgery. In the above cases

where 65% or more of the liver was removed, the

cause of death was clearly attributable to the re-

moval of too much liver. In the other 6 cases, the

only factor was the extensive hemorrhage, but as far

as the transition to a liver failure 6 patients died

within the first year after surgery, but progression to

liver damages occurred in only one case. Changes in

liver function, significant drops in Alb., and H P T in

only those cases where 2 segments of the liver had

been removed were seen in the 4th week after sur-

gery, but otherwise, there were no significant differ-

ences. In the most recent 3 years, the establishment

of operative indications, and the results of efforts to

reduce the extent of hemorrhage during surgery

have been reduced to 4 cases out of 45 cases (8.9%).

From the above, it can be seen that by the imple-

mentat ion of suitable standards for operative indi-

cations for surgery and the selection of suitable sur-

gical methods, reducing the amount of hemorrhage

during surgery, and cutting down the amounts of

post-operative hemorrhage and incomplete sutur-

ing, serious liver failures as a complication of post-

operative incompleteness can be reduced to the ab-

solute min imum, and the progression of long term

liver failures can he eliminated.

Symposium (5): Pathophysiology and clinical features of ulcerative colitis

Moderators: Mamoru NISHIZAWA and Kenzo KOBAYASHI

Prognostic assessment of ulcerative colitis from a view of radiographic findings

Atsushi KARIYA and Soko MAYAMA

Chiba Cancer Cent Hosp

Sixty patients with ulcerative colitis were followed

clinically with repeated radiographic examinat ion

long enough to assess the prognosis. Thir teen of the

60 patients had both large undermining ulcer and

longitudinal furrow at the clinical onset of the dis-

ease and eight of them underwent surgery within a

short period of follow-up. Thirty-two patients whose

ulcer was less than rice corn in size, or who had no

ulcer were not indicated to undergo surgery in the

long-term period of follow up. Therefore, morpho-

logical features at the once of the disease seem to

play an important role to prognosticate the clinical

course. Seventeen of the 60 patients (28%) showed a

changing pattern of the extent of the disease in the

follow-up period. Colonic involvement of the disease

progressed in four cases and regressed in five cases.

Moreover, the changes alternated in eight cases in

the long-term period of follow-up. In only one of the

14 patients whose lesion was initially limited to the

rectum, the left colon became involved later. From

these findings we postulate that ulcerative colitis

does not necessarily begin with at the rectum and

does not progress to involve the colon in the course

of the disease.

Natural history of idiopathic proctitis

T. MUTO, S. AGAWA, Y. KITAJIMA

and Y. MORIOKA

Dept Surg g Univ of Tokyo

Natural history of 50 cases of proctitis and 24

cases of proctosigmoiditis was studied. In proctitis

oral extension was observed in 36 % colonoscopically

and 20 % histologically whereas in proctosigmoiditis

in 16.7% histologically. Oral extension occurred

rather abruptly from proctitis to left colitis or total

colitis and gradual extension from proctitis to total

colitis was seldom observed. Oral extension tended

to occur after continuous proctitis and the longer

the follow-up period the higher the relapse fre-

quency. Out of 50 proctitis diagnosed by procto-


scopy and biopsy 49 relapsed in 4 years whereas out

of 19 non-ulcerat ive colitis type proctitis only one

was found to be idiopathic proctit is after long term

observation.

From the histochemical study of s ialomucin of the

colonic mucosa proctitis with dominan t non-acy-

lated sialomucin tended to relapse and extend orally

whereas proctitis with dominan t acylated sialomu-

cin was likely to be stable and quiescent. It was in-

teresting to note tha t Bacteroides vulgatus was most

f requent ly detected in proctitis (100 %) as compared

with in total colitis (18%).

From our observations it is concluded that idio-

pathic proctitis will extend proximal ly and is prob-

ably init ial stage of ulcerative colitis. Factors in-

f luencing oral extension of the disease are not known

a l though some al terat ions of muc in and bacter ia l

flora are present.

Reference: 1) Lennard-Jones JE, et al: Observa-

tions on idiopathic proctitis. Gut 3: 201, 1962

Medical t r e a t m e n t of u l ce ra t ive colitis

wi th re fe rence to the c l in ica l

course and severi ty

Tadash i AISAWA and Masaaki SANO

1st Dept Intern Med, Hirosaki Univ

Sch Mecl

Purpose and Subjects: Effects of medical treat-

men t to the pat ients with ulcerative colitis (UC) are

examined retrospectively. The subjects are pat ients

who admi t t ed and diagnosed as UC in our depar t -

men t f rom 1970 to 1983. Subjects are 47 males and

41 females, 88 cases in total. Ages of subjects are

f rom 13 to 63 years old with a m e a n age of 33. Ex-

tents of the lesions at first admission are 21 proctitis,

30 left sided colitis and 37 total colitis. Severity by

Truelove's classification are 43 mild, 42 modera te

and 3 severe types.

Methods and Results: Base of our medical treat-

men t is regimen by The Invest igat ion and Research

Commit tee for UC organized by the Japanese Minis-

try of Public Welfare. T rea tmen t s to 85 mild and

modera te types were oral salazopyrine (SASP) to 33

cases, SASP suppository to 5 cases, oral SASP and

steroid hormone (SH) enema to 12 cases, oral SH to

14 cases, oral SH and enema to 2 cases, oral SH and

SASP to 8 cases, SH enema or suppository to 7 cases

and others to 4 cases. T rea tmen t s to 3 severe types

were oral SH to 2 cases and oral SH and enema to 1

case. T ime to induce remission were 5.5 weeks in

oral SASP group, 7.0 weeks in oral SASP and SH

enema group and 11.9 weeks in oral SH group.

Conclusion: Remission rate at first admission was

given as high average as 93 .2%, but at second ad-

mission the ra te was 26.8%. Long te rm mainte-

nance of the remission seemed to be difficult. Medi-

cal t r ea tment to gain early induct ion and long

ma in t enance are considered.

Pathophysiology i n u lce ra t ive colit is

Nobuo H I W A T A S H I

3rd Dept Intern Med, Tohoku Univ Sch Med

Blood coagulation, fibrinolytic system, fibronec-

t in, gut hormones and pros taglandin in pat ients

with ulcerative colitis (UC) were investigated, with

reference to differences between active stage and re-

mission.

1) Blood coagulat ion: Increased fibrinogen con-

tent , factor VIII and IX activity and platelet count,

accelerated platelet aggregat ion and re tent ion rate

were found in most cases of active stage. In remis-

sion, this hypercoagulabi l i ty tended to be generally

normalized, but still r emained in a few cases. This

state may cause th romboembol i c complicat ions and

DIC syndrome, even if in remission. 2) Fibrinolytic

system: Tissue fibrinolytic activity (TFA) of the rec-

tal mucosa was examined by Todd & Nunn 's

method. There was no significant difference be-

tween TFA of active stage and tha t of normal sub-

jects (NS). However, TFA of remission was siguifi-

candy lower t han tha t of NS. 3) Plasma f ibronectin

(PFN): PFN of active stage was significantly lower

t han tha t of remission, bu t no significant differences

were ob ta ined between those and that of NS. 4) Gut

ho rmone profile: Dur ing fasting, moti l in levels of

active stage were h igher t han those of NS. The high

level of moti l in cont inued after test meal ingestion.

Enteroglucagon levels after ea t ing tended to be

h igher as compared with those of NS. At fast ing and

402 Proceedings of26thAnnualMeeting Vol. 20, No. 4

immediately following ingestion, pancreatic polypeptide levels of active stage were significantly

higher than those of NS. 5) Arachidonic acid meta-

bolism: Prostanoid synthesis by cultured rectal mucosa obtained from patients with UC was investigated. Accumulation of prostaglandin E2, throm-

boxan B,, and 6-ketoprostaglandin F,a in active stage was significantly higher than their respective

accumulation in remission. It is not definitely known that how these prostanoids play any role in etiology or pathophysiology of UC.

Pathophysiological and clinical studies in ulcerative colitis

A. KITANO and K. KOBAYASHI 3rd Dept Intern Med, Osaka City Univ

The etiology of ulcerative colitis (uc) is conserned

with many agents. We examined the coagulability, bile acid in feces, and prostaglandin (PG) level of

colonic mucosa, for the purpose of investigating the pathogenesis and clinical characteristic in uc, Peri-

pheral platelet count and its function remarkably raised in active stage.

Fibrinogen titer increased in active stage and the

chronic continuous type of uc. Fibrinolysis activity of the colonic mucosa in uc

raised as compared with healthy control. Bile acids in feces were examined with cholic acid

(CA), chenodioxycholic acid, deoxycholic acid (DCA), lithocholic acid and ursodioxycholic acid. CA increased in uc in contrast with decreased DCA. That changes of bile acid component was suggested to be caused by diarrhoea and decrease of anaero- bacterium in large bowel,

Prostaglandin PGE~ and PGI~ level of the colonic mucosa increased in uc compared with healthy con-

trol. Furthermore, that's level in active stage are higher but decreased in the introduce of inactive stage in uc. We concluded that PG were mutually

related with the inflammatory changes in colonic

mucosa.

Intestinal functional disorders related to enteric bacteria in ulcerative

colitis

Tsuneo FUKUSHIMA 2nd Dept Surg, Yokohama City Univ

In our series of ulcerative colitis, fat malabsorption was seen in 27.3% and VBI2 malabsorption was seen in 42.9 %. The patients complicated these real- absorptions revealed bacterial overgrowth in the duodenal fluid, positive free bile acid and decreased secondary bile acid in the bile.

These malabsorptions were thought to be related

to bacterial overgrowth in the small bowel. Fecal short chain fatty acids (SCFA) were investi-

gated volatile SCFA were decreased as extension of

mucosal lesion and in active stage. On the other

hand, lactic acid was increased as extension of mucosal lesion and in active stage. Volatile SCFA/lactic acid ratio was inversely related to the frequency of daily bowel movements.

Immunological study of pathophysiology and its application to the therapies

Sadakazu AISO and Hitoshi ASAKURA Dept ~Inat & Intern Med, Keio Univ

Recent studies about pathophysiology of ulcerative colitis (UC) have revealed that immunological abnormalities play an crucial role in the etiology of UC. Abnormality of population and function of sup-

pressor T cells has been reported. Many patients are complicated with thymus abnormalities where T cell

maturation process is disturbed. The presence of

auto-antibodies such as anticolon antibody and lym- phocytophilic antibody in sera from patients were

shown to be relevant to destruction of colonic mucosa, and also, the impairment of T cell lineage functions. In the treatment of UC, we must pay deep

consideration for these immunological abnormalities, and corticosteroids and immunosuppressive agents are thought to be indispensable in the treatment, esp., for the patients with high titers of auto-antibodies. The titers of anticolon antibody were demonstrated to be lowered in the patients who had been taking steroids and immunosuppressants, although the decrease is not so remarkable. More- over, patients who had undergone thymectomy showed a significant decrease of anticolon antibody titer in a few years after thymectomy. The decrease


of the antibody titer is supposed to lead the patients to a remission state. In cases which do not respond to

conventional immunosuppressive therapies, other immunological means should be taken. One of them is intra-arterial steroid injection for toxic mega-

colon, and another is administration of mast cell

stabilizers. By applying these therapeutic maneuvers which modify immunological reactions in the pa-

tients, we have succeeded in elongation of remission stage.

Reference: 1)Tsuchiya M: Gastroenterol Jpn 19: 232-246, 1984

Clinical course of surgical treatment for ulcerative colitis

Hiroshige NAKANO

1st Dept Surg, Nara Med Univ

Hundred three patients with ulcerative colitis were treated in our clinic from 1972 through 1984

and 23 patients of them (22%) were operated. In classifying the extant of the lesion, total colitis was found in 21 (91%) of the 23 patients. In classifying

the severity at operation, severe type was found in 18

(78%) of 23 patients. Fourteen (61%) of 23 patients were performed emergency operation and 9 patients

(39%) elective operation. We have treated severe case of 26 patients. The severe case is initially treated by an intensive intravenous regimen. The therapeutic effect of this regimen is evaluated within five days. Cases responsive to this regimen are subse- quently subjected either to conservative therapy or

to surgical treatment including second-stage operation. In cases in which the regimen is ineffective, emergency or urgent operation is performed. In these cases, radical operation is not performed as the first stage. Ileostomy or right-sided colostomy in- volving less surgical intervention is performed first, and after confirming improvement in general condi-

tion, radical surgery is performed. Among 23 oper-

ated cases, sphincter-saving operations of various types were performed in 19 (83%) with an annual

increase of the proportion of ileorectal anastomosis

(IRA) as the second-stage operation. Ten of 19 cases were performed IRA. As one measure to prevent anastomotic leak, we have recently performed auto-

suture using EEA on 7 cases and obtained satisfactory results.

Sympos ium (6):

Malignant lymphoma of the intestinal tract Moderators: Tatsuya YAMADA and Ikuro KIMURA

Malignant lymphoma of the gastro-intestinal tract. 1. Pathology

Koji NANBA Dept Pathol, Kure Mutual Aid Hosp and

Fac Integrated Arts ~ Sci, Hiroshima Univ

Malignant lymphomas (ML) are divided into nodal and extranodal ones according to their pri-

mary site; ML of the GI-tract is the representative of extranodal ML. Most of the extranodal ML are

characterized by the following features: (1) they arise of the preexisting lymphoid tissue, (2) 99 % are

non-Hodgkin's lymphomas and Hodgkin's diseases are quite rare, if any, (3) there are more B cell lym-

phomas compared to nodal ML. These are also ap- plicable to GI-tract lymphomas.

In childhood, most GI-lymphomas occur in the terminal ileum where Peyer's paches are well developed. Lymphoid tissues in the GI-tract play important roles for the immune defence of this organ, particularly by secretory IgA and IgM. Since the development and distribution of lymphoid tissues are significantly affected by the types and modes of anti-

genic challenges in the postnatal life, an immu- nologic point of view is essential to the understand- ing of the versatility of ML in adults with regard to sites and morphological subtypes.

Many of the gastric lymphomas are histologically

B cell lymphomas of follicular center cell type and


follicular lymphomas are not uncommon, suggesting the preceeding follicular lymphoid hyperplasia. Intestinal lymphomas are often of high grade malignancy such as immunoblastic, small noncleaved and lymphoblastic which are probably due to different pathogenesis from the gastric lymphomas.

In Japanese, 60% of GI-lymphomas arise in the stomach, 36% in small intestine and 4% in colon, whereas frigures are 33%, 50% and 17%, respectively, in American Whites. However, if ratios of lymphomas to all the malignancy in each organs are compared for both countries, it is found that incidence of lymphomas does not correlate with that of carcinomas at the same organ. Therefore, it is hard

to presume common carcinogenic factors for both

types of malignancies. Reference: 1) Kadin M, et al: Human Pathol 14:

745, 1983

Endoscopic diagnosis of gastrointestinal malignant lymphoma

Hirofumi MIYAKE* and Hideo HARADA** *2nd Dept Intern Med, Okayama Univ

Med Sch **Dept Med, Inst Thermal Spring Res,

Okayama Univ

We studied endoscopic findings characteristic of gastrointestinal malignant lymphoma (ML), and discussed the diagnostic accuracy.

Investigated were 32 patients with primary gastric ML, 17 with gastric involvement secondary to systemic ML, three with primary colonic ML and one

with colonic involvement secondary to systemic ML. Endoscopic findings were classified according to that

of early gastric cancer and also of Borrmann. In primary gastric ML Borrmann II type and III

type lesions comprised as much as 44 per cent respectively. Endoscopic observation gave correct diagnosis in only 41 per cent; about a half of lesions were mistaken for carcinoma. Endoscopic biopsy gave correct diagnosis in 53 per cent.

Combined use of endoscopic observation and biopsy gave correct diagnosis in 63 per cent. Review- ing the films of gastrofiberscope demonstrated that 80 per cent of the lesions were judged as compatible

with gastric ML, indicating that we would be able to make correct diagnosis in such a high percentage if we have the possibility of ML in mind despite its rarity.

Nine of the 17 patients with secondary gastric involvement were detected among 52 with systemic

ML in two-years' prospective study. Endoscopic

findings of the secondary gastric lesions were similar to those of primary gastric ML with exception that

the patients with secondary gastric involvement characteristically showed multiplicity of lesions and

presence of multiple small elevated lesions.

We also investigated gastric ML with endoscopic ultrasonography, which seemed to give useful information about the depth of involvement.

Although the number of patients with colonic ML, it seemed that the endoscopic findings in colonic ML were similar to those of gastric ML.

Malignant lymphoma of the gastrointestinal tract: Surgical treatment and

its results

Kunio TAKAGI

Dept Surg, Cancer Inst Hosp

A study has been made of surgical treatments for

malignant lymphoma of the gastrointestinal tract and its results. From 1946 to 1982, 96 cases of malig-

nant lymphoma of the gastrointestinal tract were surgically treated in the Department of Surgery,

Cancer Institute Hospital. 96 eases were stomach 74, small intestine 17, colon 3 and rectum 2.74 cases of

malignant lymphoma are classified in 57 single, in 7 multiple in five accompanied with malignant lymphoma of the small intestine and in four was associated with that of neck. Five-year survival rate of solitary malignant lymphoma of the stomach surgically treated was 47%, and that of radical operated cases was 61%. 5-year survival rate of early malignant lymphoma limited within submucosa was

93% (13/14). That of advanced malignant lyrn- phoma dropped to 44%. This fact shows that as in

gastric cancer the prognosis depends on the lymphnode metastases and the degree of depth invasion. In solitary malignant lymphoma, surgical treatment with dissection of lymph-node is essential. In cases


with multiple lesion, the prognosis was poor. When

accompanied with malignant lymphoma of the in-

testine or neck, these prognosis also were poor. In

malignant lymphoma of small and large bowels, all

cases were advanced, and surgical results were poor.

But chemotherapy after surgery was effective for

several five-year survival cases. We would like to

place our hope on radiation therapy and chemo-

therapy in such patients.


Prevent ion of recurrence of pept ic u lcer M o d e r a t o r s : H a r u y a O K A B E a n d Takesh i M I W A

The grade and prevention of gastric ulcer recurrence

Tsutomu IGARASHI and Youichi KURIHARA

2nd Dept Intern Med, Fukushima Med Coll

In order to know exactly the history of recurrence

of gastric ulcers, it is necessary to continue the ob-

servation of ulcer patients for about 20 years or

more. Long-term data of radiological as well as

endoscopical examinations on such cases have re-

cently been accumullated in our clinic. Based on

these observations, patients with gastric ulcer were

classified into 3 groups; i) no recurrence, ii) repeated

recurrence, and iii) the withdrawal from the re-

peated recurrence (no recurrence for more than 10

years since the final development of gastric ulcers).

Twenty-six cases with round-(shaped) gastric

ulcers which were diagnosed to have developed ini-

tially in the stomach (11 cases in the angle and 15

cases in the body) have been observed radiologically

and endoscopically for 15 to 22 years. Both ex-

aminations were performed parallel every 2 weeks in

the ulcer stage and every 6 to 12 months in the scar

stage.

Results were as follows:

1) No recurrence was obtained in 9 cases (35%)

during the long-term observation.

2) The withdrawal from the repeated recur-

rence was observed in 5 cases (19%, 35% of 17 cases

with repeated recurrence).

3) Repeated recurrence was observed in 12 cases

(46%).

4) Grade of the severity of ulcer disease, depend-

ing on the symptoms, frequencies of the recurrence

and complications, of 12 cases with repeated recur-

rence was analysed on the basis of the location of ini-

tial round ulcers. The grade was low in 5 cases of

ulcers in the body and high in 7 cases in the angle.

Factors influencing the recurrence of duodenal ulcer

Koji SUMII and Naomi UEMURA

1st Dept Intern Med, Sch Med,

Hiroshima Univ

In order to elucidate the various factors--acid

output, serum PGI, gastrin, family history, blood

type, age of onset, shape of ulcer, stress, tabacco,

alcohol, coffee and maintenance therapy--on the

recurrence of duodenal ulcer, these factors were

compared between those who recurred within 1 year

and those who did not.

A hundred and seventy-nine patients were studied

and in 42 % of patients ulceration recurred within 1

year. Age of onset, family history, acid output,

serum PGI, shape of ulcer, tabacco, stress, past his-

tory of ulcer had significant effect on recurrence.

Continuous maintenance therapy inhibited the re-

currence of ulcer in patients with increased acid

secretion, hyperpepsinogenemia I, past history of

ulcer, stress and smoking habit. In patients with

normosecretion of acid, normopepsinogenemia I

and without past history of ulcer, the rate of recur-

rence was low, even when no maintenance therapy

was performed. In patients with linear ulcer and in-

creased serum PGI levels above 150 ng/ml , the rate

of recurrence was high even when contineous main-

tenance therapy was performed.

We concluded that these factors should be con-

sidered to evaluate the efficacy of maintenance


therapy on recurrence of ulcer, because the rate of

recurrence varies by underlying conditions as above

mentioned.

Study of prophylaxis to the recurrence in gastric ulcer through long term

observation of patients with gastric ulcer or gastric

ulcer scar

Hitoshi TAKAHASHI and Rumiko NISHIGORI

Dept Oncoradiol, Cancer Cent Nara Med Univ

The purpose of this study is to define factors that

are involved in recurrence of gastric ulcer by statisti-

cal analysis of long term follow-up patients with gas-

tric ulcer or gastric ulcer scar induced by precise ex-

amination after regional mass survey of stomach.

They were examined in certain intervals by call for

re-examination using our registration system.

In cases of gastric ulcer, a total number of 382 pa-

tients (441 lesions) who were followed up more than

one year used for the analysis of recurrence in gastric

ulcer. The healing period showed a remarkable

shortening in the patients who had received continu-

ous and sufficient therapy (CT group) compared

with patients who had received intermittent therapy

(IM group). The rate of recurrence was only 4 .2%

within one year and 28.6% within a 4-years observa-

tion period in CT group. On the other hand, the

rate of recurrence was 12.5% within one year and

81.3% within 4-years observation period in IM

group. The recurrence appeared earlier and more

frequently in IM group than in CT group. From the

endoscopic point of view, rate of recurrence from

gastric ulcer scar of Sl stage showed obviously higher

than from that of $2 stage.

In cases of gastric ulcer scar (GUS), 344 patients

(383 lesion) with GUS were periodically called for

re-examination and followed up more than one

year. Gastric ulcer recurred in 23.8%. However

when the patients classified into two groups accord-

ing to endoscopic diagnosis "Sx stage" and "$2

stage", it is noticed that the recurrence rate was ob-

viously higher in the former (48.1%) than in the

latter (10.9%). Thus the endoscopic examinat ion

was supposed to be useful to predict patient's prog-

nosis. On the contrary, in the other patients diag-

nosed as GUS based on only X-ray examination, the

recurrence rate was 22.4% and no significant con-

clusion was drawn from the statistical analysis of

these patients.

Conclusion: 1) Continuous and adequate treat-

ment to the patients with gastric ulcer can decreased

the incidence of recurrence of gastric ulcer. 2) Endo-

scopic diagnosis is indispensable to know the prog-

nosis of GUS. 3) Red scar should be treated as gas-

tric ulcer because of its high recurrence rate.

References: 1) Takahashi H, et al: Follow-up

of patients given detailed examinations as requested

after mass examinat ion of the stomach. J Nara Med

Ass 27: 505, 1976.2) Takahashi H: Follow-up of Pa-

tients with Gastric Ulcer. Hepato-gastroenterology

Supplement - -A.S.N.E.M.G.E. . - - 297, 1980. 3)

Aburatani R: Following study of the gastic ulcer de-

tected by gastric mass survey. J Nara Med Ass 32:

762, 1981

Pathological physiology of recurrence of peptic ulcer and its

prevention

Hiromi SHIBATA*, Hiroshi MUTO* *,

Akinori YANAKA, Akira NAKAHARA,

Shohei KOYAMA, Hisayuki FUKUTOMI

and Toshiaki OOSUGA

*Dept Gastroenterol, Tsukubagakuen Hosp **Dept Gastroenterol, Univ of Tsuku ba

A recurrent group was compared with a non-re-

current group of the patients with peptic ulcer,

about gastric secretion, the changes of parietalcellu-

lar structures, and the adenylate cyclase activity of

the gastric mucosa.

The sensitivity of the gastric secretory function to

submaximal stimulation significantly increased in

the recurrent group.

In examining serial changes of parietalcellular

structures after a t reatment of tetragastrin, a signifi-

cant increase of the volume densities of intracellular

canaliculi was observed earlier in the recurrent

group than in the non-recurrent group.

Adenylate cyclase activity in the gastric mucosa


stimulated with histamine significantly increased in

the recurrent group. These results indicate that the sensitivity of the

parietal cells to stimulations increases in the recur-

rent group. Our study also suggests that the minor tran-

quilizer suppresses an increase of the sensitivity and prevents recurrence of peptic ulcer.

Preventing relapse of peptic ulcer

Kiyoshi KAWAKAMI and Daisuke SASAKI

1st Dept Intern Med, Hirosaki Univ Sch Med

With the advent of the histamine H2--receptor antagonists, currently peptic ulcer became one of the most easily curable diseases of the digestive tract.

According to our experience, the healing rate of peptic ulcer treated with cimetidine alone for 8

weeks was 89 %. However, the disease once healed by medical

treatment is very prone to relapse. The major clinical problem after healing is how to keep the ulcer healed.

508 patients with gastric ulcer and 216 patients with duodenal ulcer once healed by medical treatment were followed up for more than 2 years with

various medication to prevent recurrence (Mainte-

nance treatment). The follow up observation was done endoscopically.

20% of gastric ulcer and 38% of duodenal ulcer

relapsed in one year, and 35 % of gastric ulcer and 71% of duodenal ulcer relapsed in 2 years after initial ulcer healed.

As to the relation of medication used for preva- tion of recurrence to the rate of relapse, the relapse rate of patients on antianxiety drugs alone or antianxiety drugs with some antiulcer drugs, especially stimulants to mucosal defensive factors, was far lower than that of those on many kinds of antiulcer drugs without antianxiety drugs. The relapse rate was also lower in patients on sulpiride.

Moreover, we have treated some patients with autogenic taining (AT) in addition to our routine

medical therapy. AT is one of the psychosomatic therapies for psychophysiological relaxation.

The relapse rate of patients who continued AT

diligently everyday was lower than that of those who

gave up the training. Continuous practice of AT seemed to be very effective in preventing relapse of peptic ulcer.

Prevention against the recurrences of

peptic u lcerueffects of ant i - chol inergic drugs

S. HARASAWA and T. MIURA Dept Intern Med, Sch Med, Tokai Univ

In this study, we investigated the effects of anticholinergic drugs for prevention against the ulcer recurrences from a viewpoint of the gastric emptying. Our previous reports have shown that one of etiological factors of peptic ulcer may be abnor-

malities of gastric emptying, i.c. delayed gastric emptying in gastric ulcer patients, rapid gastric

emptying in duodenal ulcer patients. Oral administrations of anticholinergic drug im-

proved the abnormal gastric emptying, especially, delayed gastric emptying was normalized by ordinal doses of anticholinergics.

In gastric ulcer patients, those ulcer recurrences which were higher frequent in delayed gastric emptying cases, were significantly decreased by con- t inued treatments of anticholinergics.

In duodenal ulcer patients, those ulcer recurrences which were higher frequent in both rapid and delayed gastric emptying cases, were decreased by continued treatments of anticholinergics, but but were increased after discontinued treatments of this drug. In patients with recurrent ulcer, in spite of the treatments of anticholinergic drugs, it may be necessary not only to normalize the abnormal gastric emptying, but also to reduce the hyperacidity of gastric secretion, to decrease the serum gastrin level.

Therefore, oral administrations of anticholiner-

gics may be thought to be necessary and beneficial to prevent against the recurrences of the peptic ulcer.

Study on utility of cimetidine maintenance therapy for prophylaxis of recurrence

of gastric ulcer

Katsunori SAIGENJI* and Takeshi MIWA** *Dept Intern Med, Kitasato Univ

408 Proceedings of26th dnnualMeeting Vol. 20, No. 4

**Dept Intern Med, Tokai Univ

Aim: In order to determine whether it is possible

to control recurrence of gastrointestinal ulcer, by

maintenance therapy with cimetidine, its efficacy

was evaluated in patients with gastric ulcer by com-

paring with that of antacid.

Subjects and Methods: For cases of gastric ulcer

judged as healed endoscopically at 20 institutions in

Japan, drugs were selected at rondome by envelop

method. Test drugs used were cimetidine given at a

dose of 400 mg once daily at bed time (Group T)

and a synthetic antacid hydrotalside (Nacid) given

at a dose of 2 g once daily at bed time (Group N). As

a rule, both drugs were administered for a period of

one year continously. Endoscopy was performed at

3, 6 and 12 months after the start of treatment.

Results: A total of 305 cases (155 cases for Group

T and 150 cases for Group N) participated the trial

for prophylaxis recurrence of gastric ulcer. Out of

these cases, 255 cases (127 cases for Group T and

128 cases for Group N) completed the study. The

endoscopic cumulative recurrence rates were 7.1%

(8 cases) at 3 months and 17.1% (21 cases) at 6

months for Group T, showing significant inhibitory

effect as compared to the corresponding values of

26.8% (30 cases) and 31.7% (38 cases) for Group N

(p<0.01, and p<0.05). Although whole results have

not been obtained at present, it may be justified to

say that cimetidine maintenance therapy was effec-

tive to prolong the recurrence-free period.

T h e acce lerat ion o f basal acid ou tpu t

on the recurrence of peptic u lcer

and after a wi thdrawal of oral

admin i s tra t ion of c imet id ine , r a n i t i d i n e and pirenzepine

Susumu YAMAGATA Jr. and Hisayuki FUKUTOMI

Inst Clin Med, Univ of Tsukuba

To 6 volunteers with endoscopic normal gastric

mucosa various gastric depressants were orally ad-

ministered in usual clinical dose for 1 week. Im-

mediately after a withdrawal of cimetidine raniti-

dine and pirenzepine, the acid rebound phenomena

were shown at day ls t -3rd, but were not shown the

remarkable changes during 1 week to 1 month. Far-

thermore, we investigated the long term administra-

tion (3 month) of ranitidine. The acid rebound phe-

nomenon was recognized in the same manner as the

short term administration. However, the rebound

phenomenon was to be within the range of physio-

logical changes, because the peak values did not

show a significant difference from gastric secretion

of volunteers about the same age with endoscopical-

ly normal gastric mucosa. Acceleration of basal

acidoutput is based on the hypersensitivity of parie-

tal cells, which was considered by the results of gas-

tric secretion in the response to submaximal dose of

AOC-tetragastrin in the same volunteers.

The rebound phenomena observed within about

one week after discontinuation of various gastric de-

pressants is the result of acceleration of sensitivity of

parietal cells within the range of physiological

change, and have not direct relation with the recur-

rence of peptic ulcer which appears at a consider-

ably later stage but have the relation with the recur-

rence of acute gastric mucosal lesion or hemorrhagic

peptic ulcer.

References: 1) Yamagata S Jr, et al: Significance

of acceleration of gastric secretion in the mecha-

nisms of recurrence of peptic ulcer treated with H-

H~ receptor antagonist. Jpn j Gastroenterolo Ab p

143, Yamagata, Oct 1982.2) Yamagata S Jr, et al:

Effect of ranitidine on the 24-hour intragastric pH

changes and the time couse change after a with-

drawal of oral administration of ranitidine. Pro-

ceedings. Ranitidine Synposium, Tokyo-1984, p

90-99 Excerpta Medica, 1984

T h e m a i n t e n a n c e therapy af ter in i t i a l

treatment by ran i t ld ine

Kohei KATSUMI and Makoto ITO

1st Dept Intern Med, Nagoya City Univ Sch Med

The aim of this study is to evaluate the mainte-

nance therapy on ulcer recurrence after the initial

t reatment by ranitidine.

Method: After the completion of initial therapy

by ranitidine 150 mg twice daily, 108 gastric ulcer

(GU) and 61 duodenal ulcer (DU) patients were sub-

mit ted to receive maintenance therapy. The mainte-


nance therapy consists of ranitidine (150 mg/day)

group, pirenzepine (50 mg/day) group and placebo

group. The duration of the study was 12 months and

endoscopical observation was performed every three

months. Results: The cumulative recurrence rate in

placebo group was 65% in GU and 100% in DU

totally. The maintenance therapy by ranitidine or

pirenzepine significantly reduced the ulcer recur-

rence to 3 months in GU when compared with

placebo group, but the recurrence rates after 6

months were not significantly different among three

groups. Both ranitidine and pirenzepine significant-

ly reduced the recurrence through 12 months in DU,

though ranitidine seemed to be more effective than

pirenzepine.

Conclusion: 1) The ulcer recurrence in placebo

group was very high when initially treated by H-2

receptor antagonist. 2) Though the maintenance

therapy by ranitidine or pirenzepine reduced the

ulcer recurrence, the suppression rate were still not

satisfactory. 3) It might be difficult to achieve a

complete reduction of the ulcer recurrence by only

using an antisecretory agent after the initial treat-

ment by H-2 receptor antagonist.

Prevention of recurrence of duodenal ulcer

Masaharu T A T S U T A , Hiroyasu IISHI

and Shigeru OKUDA

Factors associated with recurrence of duodenal

ulcer and effects of cimetidine on their recurrence

were endoscopically investigated.

There was a significant effect of patient age, acid

secretion, and the extent of the acid-secreting area

and smoking on the recurrence of duodenal ulcers.

Duodenal ulcers tended to recur frequently in pa-

tients of less than 39 years old, in those with hyper-

secretion of acid, in those associated with a large

acid-secreting area and in heavy smokers.

Clinically, recurrence was significantly less fre-

quent in patients treated with cimetidine than those

with placebo. Concomitant use of cimetidine and

sulpiride prevented the recurrence of duodenal

ulcers.

On the prevention of peptic ulcer recurrence with cimetidine

maintenance therapy

M. MURAl and K. FUKUI

Dept Gastroenterol, Natl Osaka Hosp

Purpose: A study of recurrence preventive effect

of the combined use of various types of defense fac-

tor accelerators in peptic ulcer cases on cimetidine

maintenance doses.

Method: Defense factor accelerators such as

cetraxate, gefarnate, sulpiride and aldioxa were

used for combined administration in 54 peptic ulcer

cases that permitted a follow-up for 6 months or more after cure.

Results: Percentages of recurrence observed dur-

ing the follow-up period were 31% for gastric ulcer,

60% for duodenal ulcer and 33% for anastomotic

ulcer. The rate of gastric ulcer recurrence was 50%

or the highest for superior gastric ulcer. Recurrence

rates by cimetidine maintenance doses were 36 % for

200 rag/day, 43% for 400 rag/day, 25% for 600

rag/day and 0% for 800 rag/day. The higher the

maintenance dose the lower became the recurrence

rate. Moreover, no recurrence has been observed yet

in any group in and after the 9th month of follow- up.

Effect of the combined use of defense factor ac-

celerators: Recurrence rates were 67% for the non-

combined administration group, 32 % for one-drug

combined administration groups and 20% for

plural -drug combined administration groups.

Plural-drug combined use well prevented recur-

rence. Additionally, biopsy revealed fewer cases of

degeneration in the regenerated epithelia in plural-

drug combined administration groups.

Conclusion: Ulcer recurrence rate is low among

cases of cimetidine maintenance administration

combined with 2 or more defense factor accelera-

tors.

A combination therapy of peptic ulcer with ranitidine and sucralfate

Hideaki SAKAI and Yukio YOSHIDA


Dept Gastroenterol, Jichi Med Sch

We studied the relapsing rate of healed peptic ulcer during the periods of maintenance therapy (phase II) and observation (phase III). The ulcers healed in active therapy (phase I) with a combination of Ranit idine (R) (150 m g / T ) 2T + Sucralfate (S) 4 g/day are divided into three groups in phase II. The group 1 (R + S) is treated with (R)IT + (S) 2 g/day, and the groups 2 (S-I) with (S) 2 g /day for 6 months (phase II), and then observed for subsequent 6 months (phase III). The group 3 is the subgroup of the group 2, the maintenance therapy being con-

tinued for 12 months. At present, 81 patients are in phase II: DU 27

cases (group 1 9, group 2 8 and group 3 11) and GU 53 cases (group 1 20, group 2 15 and group 3 18).

Cumulative relapse rates on phase II and III are 22.2 and 88.9% in group 1, 21.1 and 62.5% in

group 2 and 45.5% in group 3 as to DU, and 20 and

60% in group 1, 36.4 and 66.7% in group 2 and 50% in group 3 as to GU.

The highest relapse rate of both DU and GU among the three groups is that of the group 1 on phase III. This may be due to the stop of Ranit idine

on phase III in group 1. The postprandial serum gastrin concentrations

measured at 2 to 8th weeks of Ranit idine administration during phase I on the same patient are 211 --- 25 pg/ml (mean _ SEM) (n=25) and 262 • 34, the gastrin level in patients with longer period of Raniti- dine uptake in group 1 being higher than those of

sucralfate in group 2 on phase II.

When the durat ion of Ranit idine uptake is relatively long in the treatment of peptic ulcer, it would

be necessary to administrate some anti-ulcer drug when Ranitidine is withdrawn.

The prevention of chronic gastric ulcer disease relapses. Clinical and experimental evaluation of combination

therapy using Histamine H2 blocker and Aldioxa

(especially with regard long term

prognosis)

Kyoichiro SUYAMA and Masaharu TSUCHIYA Dept Intern Med, Sch Med, Keio Univ

We thought principality about combinat ion therapy between Cimetidine and mucosal defensive

promoting agents. Therefore, this time we report

about investigating of Aldioxa combinated therapy.

1) Endoscopic recovery rate compared with Cimetidine single administration group (C-group)

to Cimetidine-Aldioxa combinated group (AC- group). AC-group was superior to statistical significant difference (p<0.05).

2) Cumulative recurrence rate from 6 month to 18 month distinct lower tendency in AC-group com-

pared with A-group. 3) Perioral administration of absolute ethanol

to fasting rats produced typical gastric lesions and was accompanied by the reduction of mucosal Prostaglandin E (PGE) and hexosamine level. Pre- treatment with PGE2 and Aldioxa prevented the formation of gastric lesions and restored mucosal PGE and hexosamine level. There was a negative correlation between the level of mucosal PGE and

the degree of gastric mucosal lesions. 4) In clinical study using biopsy materials ob-

tained by endoscopy, we were not distincted significant to PGE and 6-keto-PGFIa activity tripartite C- group, A-group (Aldioxa single administration) and

AC-group. However, PG activity distincted signifi-

cant reduction with healing of ulcer stage.

On the maintenance therapy of peptic ulcer patients with a single bedtime

dose of cimetidine

Takashi NAKAMURA and Sen KO 1st Dept Med, Teikyo Univ

Two hundred and eighty-one peptic ulcer patients were mainta ined with a single bedtime dose (400 mg) of cimetidine for prevention of ulcer recurrence, and were checked endoscopically every 3 months. Overall recurrence rates were 9.4% in 3 months, 21.7% in 6 months, 28.7% in 9 months and 30.7% in a year. Among these cases, recurrence

rates of groups, of which healing with conventional ulcer therapy or with cimetidine therapy was de-

layed, were much higher than those of the other


groups, and those of remained healed group or of

easily healed group were lower than those of control

group. Healing rate of recurrent cases with this mainte-

nance therapy was very low even by full dose cimeti-

dine therapy.

This maintenance therapy seems to be very effec-

tive if patients are selected.

Studies on the relapse rates of peptic

ulcer grouped by adminis t ra t ion

method of h is tamin H2 receptor antagonist

Masanobu SATO and Atsushi KANO

1st Dept Intern Med, lwate Med Univ

The relapse rates of peptic ulcer (gastric ulcer-

GU: 81 & duodenal ulcer-DU: 41) in whom endo-

scopy could be performed every three months after

recovery were studied, classified by administration

method of histamine H2 receptor antagonist (H2-

blocker).

The relapse rates up to 12 months were 41% in

GU and 52% in DU.

The relapse rate in the combined therapy group

was lower than that in the single H2-blocker group.

Almost no relapse was observed in the cases in whom

800 m g / d cimetidine was given continuously after

recovery. On the other hand, a few cases showed re-

lapse when the amount of cimetidine was decreased

to 400 mg/d . In the cases in whom no administra-

tion of H2-blocker after recovery was given high re-

lapse rates (41% in GU & 55% in DU up to 6

months) were observed.

The relapse rate, in the cases in whom cimetidine

was discontinued after decreased amount of 400

m g / d of cimetidine was administrated during 6

months after recovery, was lower than that in the

cases in whom H2-blocker was suddenly discon-

tinued after recovery.

Cimetidine maintenance therapy for stomal ulcer by a patient-month

observation

Ken-ichi YUKAWA

Yukawa Gastrointestinal Hosp

In the long-term follow-up study of peptic ulcer

disease, as already pointed outX), there are problems

of compliance with respect to medication and at-

tendance for serial endoscopy. Here we present re-

sults of cimetidine maintenance therapy for post-

operative stomal ulcers by pat ient-month observa-

tion to solve the problems. After the ulcer had

healed, cimetidine dose was decreased from 800 mg

to 400 mg then 200 nag. Once stomal ulcer recurred,

800 mg cimetidine therapy was done. After the ulcer

healed, next maintenance therapy was restarted de-

creasing the dose down to the previous maintenance

dose. Among 24 cases, 21 had periods of both good

and poor compliance in the course. This makes it

possible that average durat ion for one recurrence in

the period of good drug compliance was estimated

comparing to that in the period of poor drug com-

pliance.

Results: Average duration for one recurrence was

37 months in the period of good compliance (14 re-

currences 221 endoscopies in 514 patient-months) in

contrast to 14 months in the poor compliance (22 re-

currences 68 endoscopies in 312 patient-months)

(statistically significant). In the period of poor com-

pliance, as average interval of endoscopy was

longer, the time to confirm the recurrence tends to

delay. But the average duration for one recurrence

was longer enough in the period of good compli-

ance. In the period of good compliance, patient-

months of maintenance dose of 400 mg and of 200

mg were enough in number and with these dose it

was possible to prevent the recurrence well in prac-

tice.

Conclusion: Cimetidine maintenance therapy

after stomal ulcer healed is thought to prevent

further recurrence. The maintenance dose may be

enough to be 400 rag. In the long-term follow-up

study it is important to know the drug compliance

and frequency of examination.

References: 1) Meyrick Thomas J, Misiewicz G:

Histamine H2-receptor antagonists in the short and

long-term treatment of duodenal ulcer, Clinics in

Gastroenterology, 515 Vol 13 No 2, May, 1984.

W.B, Saunders Company


Symposium (8):

Current status of functional control of the small bowel Moderators: Zen I T O H and Akira YACHI

Correlations existing between the duodenum and other organs in

terms of gastrointestinal hormones

T. YABANA and A. YACHI Dept Intern Med (Sect I),

Sapporo Med Coil

In order to clarify the pathogenetic and pathophysiological features of gastric and duodenal ulcers

(GU and DU), correlations between the duodenum distributed by various endocrine cells and other

digestive organs were investigated in terms of plas-

ma secretin and gastrin release. The results were as follows:

1) Plasma secretin response to intraduodenal

HC1 stimulation (pH 3, 2 and 1 in tern) increased in parallel with gastric acid output (AOP) in control and GU patients whereas these phenomena were not clearly observed in DU patients.

2) The plasma secretin response was significantly higher in the active stages than that in the scarring stages of DU patients.

3) Plasma gastrin levels were definitely inhibited by the intraduodenal HCI stimulation in controls whereas such a remarkable decrease was not observed in GU and DU patients.

4) Pancreatic bicarbonate secretions were found to be correlated significantly with gastric AOP in the

active stages of DU patients but not in the scarring

stages. 5) A significant release of endogenous secretin

was found in control rats after the intraduodenal

HC1 stimulation. However, these responses were not observed in the cysteamine-induced DU model rats.

These findings suggested that there were low or impaired plasma secretin responses to the intraduodenal HC1 stimulation and impaired correlations between duodenum and other digestive organs including GEP correlations. In addition, an insuffi- cient inhibition of gastrin and gastric acid secretions

might result in a failure of the alkaline condition of the duodenum.

Regulation of the gastrointestinal motility in interdigestive state

Hideki NODA and Takayoshi TOBE*

Dept Surg, Shiga Pref Med Cent Adult *1st Dept Surg, Fac Med, Kyoto Univ

It is well known that in interdigestive state, cyclic

motor activity, so called "interdigestive caudad- migrating myoelectric complex (IMMC)" occurs in the alimentary canal.

In our experiments: IMMC was inhibited by feeding and injection of gastrin, but not by secretin and motilin. Plasma motilin levels were synchronized with cyclic motor activity and exogenous motilin induced IMMC like contractions. On the other hand, plasma gastrin levels were falling gradually after meals and were low levels without fluctuation in

interdigestive state. IMMC was also observed in truncal vagotomized

dogs (TV), but the initiation of IMMC was delayed after feeding. The frequency of IMMC and contractions decreased and the duration of IMMC became

longer after truncal vagotomy. Biphasic gastric

motor activities, inhibitory (phase 1) and excitatory (phase 2) phase were observed by injection of insulin. The excitatory phase consisted of atropine re-

sistant contractions and contractions inhibited by

atropine. When insulin was infused in the state of IMMC, contractions were abolished in phase 1, then appeared again in phase 2. In TV and control groups, IMMC was inhibited by injection of atropine.

Duration of IMMC became shorter and plasma motilin levels with fluctuation were suppressed by continuous infusion of glucose, but IMMC was not always inhibited by injection of small dose of glucose. Inhibition of IMMC occurred only in the state of low levels of plasma free fatty acid (FFA). Plasma


FFA levels declined after intravenous hyperali- mentation (IVH) and rised during fasting. During fasting, contractions continued throughout the ob-

servation period and the plasma motilin levels showed high. Conversely, after IVH, gastric motor

activity was quiescent and the plasma motilin levels

showed low. Gastric emptying time was not affected by injection of gastrin, secretin and motilin, but

suppressed by IVH and vagotomy, and accelerated

by starvation. In conclusion: Motilin may play an important

role in inducing IMMC and the state of starvation is an important condition for the appearance of IMMC. Cyclic appearance of IMMC is independent on vagal nerve which regulates the contractions

from inhibitory and excitatory sides.

Neuropeptides and contractile motility of the small intestine

Toku TAKAHASHI and Takehira YAMAMURA 2nd Dept Surg, Hyogo Coll Med

Recent immunohistochemical studies indicate the

presence of a number of biologically active neuro-

peptides in the intestinal wall and they are assumed to modulate intestinal motility1). We studied various

neuropeptides induced contractile motility and SH- acetylcholine (Ach) release of the guinea pig ileum

using the standard organ bath technique and superfusion system~.S). Neurotensin (NT), Bombesin

(BBS) and Cholecystokinin octapeptide (CCK-OP) evoked contractions were significantly reduced by atropine, and almost completely abolished by tetro- dotoxin (TTX). On the other hand, atropine or TTX reduced the recovery phase to the base line of Substance P (SP) without affecting the initial contractions, suggesting the SP, apart from its direct action on the smooth muscle, may activate cholinergic neurons. There was a remarkable increase of SH-

Ach release by the superfusion of NT, BBS, CCK- OP and SP in a dose dependent manner

(10-9M-10-7M), which was significantly reduced

by TTX or Ca-free medium. Hexamethonium had

no effects both on contractions and SH-Ach release

of these peptides. Desentitization to SP reduced the responses of NT, BBS and CCK-OP, and abolished

the atropine-resistant contractions of these peptides.

It was suggested, therefore, that contractions evoked by NT, BBS and CCK-OP were mediated by not only Ach but also SP release from the myenteric

plexus. References: 1) Schultzberg M, et al: Neurosci-

ence 5: 689-744, 1980. 2) Kusunoki M, et al: AmJ Physiol 246: R502-R509, 1984. 3) Takahashi T, et al: Dig Dis Sci 29: 87S, 1984

Local release of VIP from canine small intestine

Tadashi MISAWA and Hiroshi IBAYASHI 3rd Dept Intern Med, Fac Med, Kyushu Univ

The release of vasoactive intestinal polypeptide (VIP) from the small intestine was investigated after

the administration of test solutions into the ileum

and intravenous infusion of caerulein in anesthe- tized dogs. The levels of plasma immunoreactive VIP were measured by radioimmunoassay method1).

The basal mean plasma IR-VIP levels in the jeju- nal vein, ileal vein, pancreaticoduodenal vein and right colonic vein were significantly higher than those in the left gastroepiploic vein and femoral vein. A significant release of VIP was observed by the administration of 100 ml bovine bile (pH=7,300 mOsm/1), but not by 5% glucose, amino acids and lipide). Intravenous infusion of caerulein (1.2 ug/kg) produced a marked release of VIP from the jejunum and ileum. These marked responses of VIP, induced by bile and caerulein, were blocked by atropine (2 mg/kg iv), but not by hexamethonium (15 mg/kg

iv). These results suggest that the local release of VIP

from the small intestine is transmitted via muscari-

nic receptors. References: 1) Chijiiwa Y, Misawa T, et al: Study

of vasoactive intestinal polypeptide. 2. The release of VIP from the canine small intestine. Syokakan Horumon 4: 332, 1984.2) Chijiiwa Y, Misawa T, et al: The release of vasoactive intestinal polypeptide from the canine ileum. Igaku No Ayumi 126: 234,

1983


Pept idergic nerves in the intest inal

t ract

S. KISHIMOTO and S. SHIMIZU

Dept Med, Hiroshima Univ

Peptidergic nerves were widely distributed in the

gastrointestinal wall of human and animals. This

suggests that such nerves contribute to some func-

tion of the gut and its changes in gut disorders. In

this study, we have performed to know the change in

immunocytochemical distribution of such nerves

(VIP, NPY) in the intestinal wall of patients with

Crohn's disease (CD), megacolon (MC), and ulcera-

tive colitis (UC). Absence of peptidergic nerves was

found in contracted and strictured segment of intes-

tine in both CD and MC. On the contrary, reac-

tivities of VIPergic nerves were increased in the di-

lated segment of the colon in MC, pathologically

almost normal segments of the ileum in CD and of

the colon in UC. The results suggested that the pep-

tidergic nerves could modify the characteristic signs

and symptoms of these disorders.

Regula t ion of intest inal moti l i ty by

intrinsic nerve plexuses

Syogoro NISHI

Dept Physiol, Kurume Univ Sch Med

The intrinsic nerve plexus of the intestine reflexly

regulates the contraction of smooth muscles. As the

intraluminal pressure is raised there will be progres-

sive excitation of afferent neurons. They are as-

sumed to be Type II or AH neurons known to gener-

ate a long-lasting afterhyperpolarization. Their

synaptic responses are characteristically slow and

have no nicotinic component - - the fast excitatory

postsynaptic potential (EPSP). The afferent im-

pulses that eventually produce descending inhibition

are transmitted through interneurons to the final in-

hibitory neurons which may be purinergic. The

interneurons are Supposed to be Type I or S neurons

which have properties quite similar to the extra-

mural autonomic ganglion cells. Descending inhibi-

tion is followed by descending excitation with a time

lag of 2 to 11 seconds (guinea-pig ileum). This

marked delay has been suggested to result from a

temporary blockade of the descending excitatory

pathway, which is synaptically induced by the pre-

ceding impulses in the descending inhibitory path-

way. An alternative explanation of the delay is that

the descending excitatory pathway contains one or

two Type II neurons in which the EPSP takes several

seconds to attain a liminal amplitude.

Morphology of the enteric nervous system

Terumasa KOMURO and Yasuo UEHARA

Dept Anat, Ehime Univ Sch Med

The enteric nerve plexus of the rat and the rabbit

are studied by scanning and transmission electron

microscopy. The myenteric plexus consists of gan-

glia and interconnecting nerve fibres which show

peculiar arrangement depending on a different seg-

ment of the digestive tract. The submucous plexus

contains smaller ganglia and show looser arrange-

ment in comparison with the myenteric plexus. The

enteric ganglia are composed of compact aggrega-

tions of neurons, glial cells and their processes which

formed the neuropil. The ganglia display several

features which are known to be characteristic of the

central nervous system, but not of other peripheral

ganglia as spinal and sympathetic ganglia. The

outer surface of the ganglia are covered with a con-

tinuous basal lamina, and neither connective tissue

nor blood vessels are found inside the ganglia. Neu-

rons are imcompletely surrounded by other compo-

nents and large parts of their cytoplasm extended

directly to the basal lamina surrounding the gan-

glia. About one third of the total surface area of the

myenteric ganglia are occupied by neuronal cell

membrane. The majority of non-neuronal ceils in

the ganglia show the similarity to fibrous astrocytes

of central nervous system. Some of non-neuronal

cells are found to be resembled central nervous sys-

tem microglia. Six main types of axon plofile are

classified on a morphological consideration of the

vesicle populat ion and the difficulties relating axon

type to putative transmitters are discussed. It is sug-

gested that the structural features of the interstitial

cells (of Cajal) are different from those of neurons,

Schwann cells, or of smooth muscle cells, while they

show clear similarity to those of fibroblasts.


Enkephalin neurons in the duodenum

S. KOBAYASHI, M. SUZUKI, T. UCHIDA* and N. YANAIHARA**

*Dept Anat, Yamanashi Med Sch, Yamanashi * *Lab Bioorganic Chem, Shizuoka Coll Pharm

An antiserum (R-0171) to methionine-enkephalin-Arg6-GlyT-Leu s (Met-Enk-Arg-Gly-Leu) was ap-

plied for the investigation of the occurrence, dis-

tribution and ultrastructure of nerve elements con- taining opioid peptide-like immunoreactivity (enk-

ephalin neurons) in the guinea pig duodenum. Whole mount preparations of duodenal tissues per-

fusion-fixed with Bouin's fluid were immunostained by the peroxidase-antiperoxidase method. Many

perikarya in the myenteric plexus showed different degrees of Met-Enk-Arg-Gly-Leu-like immunoreactivity. The morphology of these enkephalin neurons varied from cell to cell. There were immuno-positive Dogiel type 1 (characterized by short, broad dendrite-like processes and a single, long axon-like process), Dogiel type 2 (characterized by smooth peri- karyon and a few tapering processes) and Dogiel

type 3 neurons (characterized by dendrite-like processes branching around other ganglion cells). The single axon-like process of many Dogiel type 1 neurons were anally directed and ran in the primary

fasciculi across the ganglia. Non-varicose processes and beaded terminals of the enkephalin neurons

existed not only in the myenteric plexus but also in

the longitudinal muscle layer, in the circular muscle layer, in the deep muscular plexus, in the submu-

cous plexus, in the muscularis mucosae and around the duodenal gland. No immuno-positive perikarya

were demonstrated in the submucous plexus. Few nerve elements in the perivascular plexus and in the mucosa showed immunoreactivity. In the electron microscopic immunocytochemistry by the protein A- colloidal gold method, immunoreactive Met-Enk- Arg-Gly-Leu was demonstrated in the large-cored vesicles of the nerve fiber varicosities and the perikarya. Enkephalin-immunoreactive nerve terminals formed synapses with either immuno-positive or immuno-negative perikarya in the myenteric plexus.

Reference: 1) Kobayashi S, et al: Biomed Res 5/6, 1984

Proceedings of the 26th annual meeting Chiba, Japan, October 18–20, 1984

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