26
August 1981 Proceedings of 22nd Autumn Meeting 399 Symposium (1): Immunological Aspects of Chronic Liver Disease: Co-Moderators: Dr. Hideo NAGASHIMA and Dr. Kenichi ITO Abnormality of serum immunoglobulins in chronic liver disease --immune complex like substances, abnormaly basic y- globulin, secretory IgA and anti-DNA antibody-- Terukatsu ARIMA and Hideo NAGASHIMA The First Department of lnternal Medicine, Okayama University Medical School 1) Serum secretory IgA was reduced in chronic liver disease while it was increased in obstructive jaundice. 2) Serum anti-dsDNA antibody was slight- ly increased in chronic liver disease, especially it was significantly increased in lupoid hepatitis in which its titer paralelled with the course of disease activity. 3) Serum Clq binding activity, Clq binding inhibi- tion activity and polyclonal rheumatoid factor bind- ing inhibition activity were increased in chronic liver disease and their disease activity was correlated with concentration of macromolecular immune com- plexes which were fractionated with sucrose density gradient ultracentrifugation. 4) Abnormally basic y-globulin which was dominantly found in chronic hepatitis B sera was determined to be monomeric IgG. It was increased in aggravation of the disease but has no correlation with Clq binding monomeric IgG. 5) Liver membrane specific lipoprotein (LP-1), Espinosa's liver specific antigen (LSA), Nerenberg's hepatorenal antigen (HRA) and Tamm-Horsfall glycoprotein (THGP) had positive charge, and LP-2 and F-antigen did negative charge. 6) Human liver cell membrane fraction could not be obtained by the method of Ray or aqueous two phase polymer system which have been used for rat liver. The specificity of sera from patients with chronic active hepatitis and the clinical significance of the determination of their ADCC activity Kunihiko ISHITANI and Ichiro URUSHIZAKI The Fourth Department of Medicine, Sapporo Medical College In this study we investigated the antibody depen- dent cell-mediated cytotoxicity (ADCC) of lympho- cytes from normal human blood against Chang liver cell (CLC) and J-III (which is a human monocytic leukemia cell line) in the presence of patients' sera with liver diseases. We observed a quite higher posi- tive ratio of ADCC activity in the culture system of CLC as a target cell than that of J-III as a control target cell. In addition, by immunofluorescent study using rat liver, kidney, intestine, the specific anti- body to liver cell was found in these sera. Further- more, sera which was absorbed with CLC reduced ADCC activity. From these results, we considered that there was a specific antibody to the liver cell in the ADCC positive sera of patients with liver dis- eases. Using this assay system, positive ratio of ADCC activity was very high in the sera of chronic active hepatitis (CAH). In cases with CAH, high ADCC activity was observed before transaminase value increased, and the corelation between ADCC activity and transaminase value was seen during clinical course. The study of serum ADCC activity may be a useful parameter in autoimmune process of hepatitis. Study of immunological mechanism in the pathogenesis of chronic liver diseases Mikio ZENIYA, Hiroshi TAKAHASHI and Yoshio AIZAWA The First Department of Internal Medicine, Jikei University School of Medicine Cytotoxic mechanism of liver damage by lympho- cytes of chronic liver diseases was studied. Serum from the patients suffered by chronic liver

Abnormality of serum immunoglobulins in chronic liver disease—immune complex like substances, abnormaly basic γ-globulin, secretory IgA and anti-DNA antibody

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August 1981 Proceedings of 22nd Autumn Meeting 399

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

I m m u n o l o g i c a l Aspects of C h r o n i c L i v e r Disease:

Co-Modera tors : Dr. Hideo N A G A S H I M A and Dr. Kenichi I T O

Abnormali ty of serum immunoglobulins in chronic liver disease - - i m m u n e complex

like substances, abnormaly basic y- globulin, secretory IgA and

ant i -DNA an t ibody- -

Terukatsu ARIMA and Hideo NAGASHIMA

The First Department of lnternal Medicine, Okayama University Medical School

1) Serum secretory IgA was reduced in chronic liver disease while it was increased in obstructive jaundice. 2) Serum anti-dsDNA antibody was slight- ly increased in chronic liver disease, especially it was significantly increased in lupoid hepatitis in which its titer paralelled with the course of disease activity. 3) Serum Clq binding activity, Clq binding inhibi- tion activity and polyclonal rheumatoid factor bind- ing inhibition activity were increased in chronic liver disease and their disease activity was correlated with concentration of macromolecular immune com- plexes which were fractionated with sucrose density gradient ultracentrifugation. 4) Abnormally basic y-globulin which was dominantly found in chronic hepatitis B sera was determined to be monomeric IgG. I t was increased in aggravation of the disease but has no correlation with Clq binding monomeric IgG. 5) Liver membrane specific lipoprotein (LP-1), Espinosa's liver specific antigen (LSA), Nerenberg's hepatorenal antigen (HRA) and Tamm-Horsfall glycoprotein (THGP) had positive charge, and LP-2 and F-antigen did negative charge. 6) Human liver cell membrane fraction could not be obtained by the method of Ray or aqueous two phase polymer system which have been used for rat liver.

The specificity of sera from patients with chronic active hepatitis and the

clinical significance of the determination of their

ADCC activity

Kunihiko ISHITANI and Ichiro URUSHIZAKI The Fourth Department of Medicine, Sapporo

Medical College

In this study we investigated the antibody depen- dent cell-mediated cytotoxicity (ADCC) of lympho-

cytes from normal human blood against Chang liver cell (CLC) and J-III (which is a human monocytic leukemia cell line) in the presence of patients' sera with liver diseases. We observed a quite higher posi- tive ratio of ADCC activity in the culture system of CLC as a target cell than that of J-III as a control target cell. In addition, by immunofluorescent study using rat liver, kidney, intestine, the specific anti- body to liver cell was found in these sera. Further- more, sera which was absorbed with CLC reduced ADCC activity. From these results, we considered that there was a specific antibody to the liver cell in the ADCC positive sera of patients with liver dis- eases. Using this assay system, positive ratio of ADCC activity was very high in the sera of chronic active hepatitis (CAH). In cases with CAH, high ADCC activity was observed before transaminase value increased, and the corelation between ADCC activity and transaminase value was seen during clinical course. The study of serum ADCC activity may be a useful parameter in autoimmune process of hepatitis.

Study of immunological mechanism in the pathogenesis of chronic

l iver diseases

Mikio ZENIYA, Hiroshi TAKAHASHI and Yoshio AIZAWA

The First Department of Internal Medicine, Jikei University School of Medicine

Cytotoxic mechanism of liver damage by lympho- cytes of chronic liver diseases was studied.

Serum from the patients suffered by chronic liver

400 Proceedings of 22nd Autumn Meeting Vol. 16. No. 4

disease evoked the antibody dependent cell-medi- ated cytotoxicity (ADCC) to the isolated rat hepato-

cytes by normal lymphocytes.

Cytotoxicity to autologous isolated hepatocytes was also seen in lymphocytes of chronic hepatitis.

On the other hand K-cell (effector of ADCC) of

chronic hepatitis show the decrease in peripheral

blood measured by the plaque method using sheep

red-blood-cell as a target cell. One of the cause of this decrease is shown to be

that serum from chronic hepatitis plays as a blocker of Fc-receptor on K-cell.

Conclusion: In chronic hepatitis ADCC plays one of the cause of chronic liver cell destruction. In serum there was some factors which evoked and in-

hibitted the K-cell function.

Immunological study of mechanism of liver cell in jury in chronic liver diseases

Kiyoshi ISHIHARA and Fumihiro ICHIDA The Third Department of Internal Medicine,

Faculty of Medicine, Niigata University

For the purpose of clarifying the mechanism of

liver cell destruction in chronic liver diseases, we in- vestigated the cytotoxicity of autologous or allo-

geneic lymphocytes to short-term cultured hepato- cytes, isolated from liver biopsy specimens, in micro- cytotoxicity assay. These cultured hepatocytes were proved to possess albumin or HBsAg in the cyto- plasm by immunofluorescence techniques, and bear HLA antigens on the cell surface by direct cytotoxic

test. When autologous lymphocytes were used as

effector cells, more cytotoxic effect of T cell fraction was observed in 10 out of 13 cases. In other 3 cases % cytotoxicity of total lymphocytes was relatively low and their histological changes were almost simi- lary mild. These data suggest that T cell mediated cytotoxicity mainly contributes to liver cell injury in

chronic liver diseases.

When allogeneic lymphocytes were used, non T cell fraction was generally showed to be more cyto-

toxic than T cell, suggesting that the effector cells

involved may possibly belong to K cell or NK cell population. On the contrary, significantly higher

cytotoxicity in T cell was observed in certain com- binations. In these groups there were partial iden-

tities of HLA-A or -B antigen between lymphocyte and hepatocyte donor and those lymphocytes were proved to be positive in LMT with HBsAg. These findings suggest that there may be HLA restriction

of cytotoxic T cell lysis of HBV infected hepatocytes, as has been demonstrated in recent studies of the human cytotoxic response to the male antigen, di- nitrophenol and influenza virus.

Immunological studies on the chronic active hepatitis

Yasuhiro MIZOGUCHI and Takeyuki MONNA The Third Department of lnternal Medicine,

Osaka City University Medical School

The possible involvement of cell-mediated im- munity in the pathogenesis of chronic active hepati-

tis (CAH) was investigated. The peripheral blood lymphocyte from all these patients showed the posi- tive lymphocyte transformation when stimulated with liver specific lipoprotein (LSP).

Macrophage activating factor (MAF), a kind of

lymphokines, was also detected in 69.5% in the cul- ture medium of LSP-activated lymphocytes. The MAF-activated macrophage and the culture super- natant of them were shown to be cytotoxic to the separated liver cells by judging their inhibitory effect on the albumin biosynthesis.

On the one hand, the antibody to liver cell mem-

brane was detected in 51.2% in sera by an antibody- dependent cell-mediated cytotoxicity (ADCC) test. Chemical mediator which was produced by K-cell in

ADCC reaction, was shown to be cytotoxic to the

separated liver cells by judging their inhibitory effect on the albumin biosynthesis. K-cell popula- tion in peripheral lymphocyte was analysed with a microscale method using ADCC reaction. The level of active cells in ADCC reaction was shown to be sig- nificantly lower in the patients than those of normal individuals. Although the level of K-cell population

was lowered by impairing function of the monocyte with slica treatment, the addition of supernatant of macrophage culture caused an apparent increase of K-cell population.

August 1981 Proceedings of 22nd Autumn Meeting 401

These results suggest that macrophage-mediated

cytotoxicity and ADCC may play a role in the patho- genesis of CAH.

Cellular immune responses to bile antigens in PBC and other intrahepatic

cholestasis

Masahiko ADACHI and Yasuro YAMAMOTO* The Second Department of Internal Medicine,

School of Medicine, Kyoto University, Kyoto

*The First Department of Internal Medicine, Kochi Medical School, Kochi

Cell-mediated immune responses to bile antigens

have been demonstrated, using the leucocyte migra- tion inhibition test (LMIT). The bile antigens were prepared by the method previously described. In- hibition of leucocyte migration in the presence of bile antigens was observed in 18 (94%) of 19 patients

with PBC, in 9 (41%) of 22 patients with other intrahepatic cholestasis, and in 3 (30%) of 10 pa-

tients with extrahepatic cholestasis. In these 3 pa- tients, there were 2 patients with primary sclerosing

cholangitis. The bile antigens were composed of at least 3 antigens and revealed, by immunofiuores-

cence method, that some of them were derived from bile duct epithelial cells. To investigate further

characterization of bile antigens, the 1st peak of

Sephadex G50 was subjected to gel filtration on Sepharose 6B. Between the third-fifth peaks the three bile antigens were" eluted. Using each bile anti- gens, LMIT was performed. Inhibition of leucocyte migration in the presence of bile antigen with an ap- proximate molecular weight of 7 x 10~ was observed 7 of 8 patients with PBC. It was suggested that cellu- lar immune response to the bile duct epithelial anti- gens play an important role in the pathogenesis of PBC.

References

1) Eddleston ALWF, et al: Brit MedJ 4: 274, 1973

2) Sano Masaju, et al: Acta Hepatol Jpn 19: 835, 1978

3) McFarlane IG, et al: Gastroenterology 76: 1333,

1979

Suppressor and helper cell activity in patients with chronic hepatitis

Akitaka NONOMURA, Mikio TANINO*, Yasuhiro KATO and Kenichi KOBAYASHI**

Department of Pathology * and Internal Medicine **, Kanazawa University

Both spontaneous suppressor or helper T cell ac- tivity present in the peripheral circulating lympho- cytes and Concanavalin A (Con A)-induced suppres- sor T cell activity were investigated in patients with chronic hepatitis and healthy subjects. The sponta- neous suppressor or helper T cell activity was evalu-

ated by measuring the capacity of T cells to help differentiation of B cells into plasma cells in re-

sponse to pokeweed mitogen (PWM) with increasing ratio of T:B in vitro culturO.2). Peripheral T cells of

patients with chronic active hepatitis (CAH) showed

a significantly decreased suppressor effect (or in-

crease helper effect) on allogeneic B cell differentia- tion into Ig-producing cells, when compared to

healthy subjects (p<0.001). After irradiation of T cells to eliminate suppressor cell influences and to evaluate genuine helper activity, helper activity of CAH was not different from that of healthy subjects, suggesting that spontaneous helper cell activity of CAH was normal, whereas spontaneous suppressor cell activity was significantly decreased. Further- more, Con-A induced suppressor cell activity both on allogeneic B cell differentiation into Ig-pro- ducing cells in the presence of PWM 2) and on al- logeneic lymphocyte blast transformation response

to Con A 3) was significantly decreased in patients with CAH, when compared to healthy subjects

(p<0.001). Similar Con-A induced suppressor cell defect was also observed in patients with chronic persistent hepatitis (CPH), but lesser degree

(p<0.05). There was no clear cut difference in sup- pressor cell activity between patients with and with- out HBs antigen in the serum. These results suggest that decreased suppressor T cell activity may reflect more or loss disease activity of chronic hepatitis and altered immune responses of CAH regardless of the presence of serum HBs antigen.

402 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

References

1) YataJ:JpnJAllergo126: 17, 1977 2) Kuritani T, et al: Microbiol Immunol 23: 185,

1979 3) Hodgson HJF, et al: Clin exp Immunol 32: 451,

1978

Loss of suppressor T cell function and cir-

culating immune complexes in chronic active liver diseases

Shinichi KAKUMU and Ryo HOTTA

The Third Department of Medicine, Nagoya University School of Medicine

To approach the question as to why patients with chronic active liver disease (CALD) have a defect in the development of suppressor T cells, we examined the effect of sera from patients with various liver dis- eases on concanavalin A (ConA) induced suppressor T cell activity of normal individuals. Suppressor T cell activities were inhibited by pretreatments with 13 of 27 heat-inactivated sera from patients with CALD and 5 of 11 sera from patients with acute

viral hepatitis, whereas no sera from 18 patients with other liver diseases affected suppressor cell ac- tivity. The addition of heat-aggregated human IgG

eliminated normal suppressor activity. In contrast, normal suppressor activity was induced when im-

mune complexes in sera of CALD patients were re- moved with polyethylene glycol. There was a signifi-

cant correlation (p<0.01) between bloc'king against

the development of suppressor T cell and the level of

circulating immune complexes in CALD patients' sera when 125I-Clq binding test was used. These data

suggest that circulating immune complexes modu- late cellular immunity in patients with CALD by im- pairing suppressor T cell function.

Analysis of immunity in patients with chronic hepatitis by use of autologous MLR

Tetsuo SHINGAMI and Shuji HASHIMOTO

The Second Department of Internal Medicine, Faculty of Medicine, Kagoshima

University

Autologous mixed lymphocyte reaction (AMLR),

in which non-T cells stimulate proliferation of auto-

logous T lymphocyte, are thought to represent a

self-regulatory immune mechanism.

AMLR function, AMLR and Con A induced sup-

pressor cell activity were measured in patients with chronic hepatitis. As the result, AMLR function was significantly depressed in patients with chronic ac- tive hepatitis (CAH) and chronic inactive hepatitis (CIH). AMLR and Con A induced suppressor cell activity were significantly depressed in patients with CAH and CIH. AMLR function and AMLR in- duced suppressor cell activity had relation to disease activity. Non-T cell function of patients with CAH was normal but T cell function was disturbed. These findings suggested that AMLR dysfunction in pa-

tients with CAH was caused by T cell dysfunction. T cells of healthy volunteers, treated with plasma

of patients with CAH plus complement could not re- spond to autologous Non-T cells. These findings

suggested that antibodies to T cells present in the

plasma of patients with CAH. It was shown by sephadex G-200 column chromatography that this

antibodies belong to Ig G class.

References

1) Shingami T, Tsuji K: Analysis of reactive system in autologous MLR. Digestive organ and Irn-

munology No. 5, 19-23, 1980 2) Shingami T, et al: Immune function in patients

with ulcerative colitis. Digestive organ and Im- munology No. 5,100-104, 1980

3) Shingami T, et al: Autologous MLR function in patients with chronic hepatitis. Digestive organ and Immunology No. 6, 1980. (in press)

Lymphocyte-mediated enhancement of colla-

gen production in hepatic fibrosis ~Detection of fibrogenesis ehnancing activity in lymphokine from LSP and

HBsAg-stimulated lymphocytes in patients with chronic active

hepatitis--

Hiroshi NAKANO and Tomoyoshi SUGIYAMA The Second Department of lnternal Medicine,

School of Medicine, Kyoto University

August 1981 Proceedings of 22nd .4 utumn Meeting 403

As several lymphokines play important roles in chronic inflammatory processes, we studied the fibrogenic activity in cultured supernatant of peri- pheral blood lymphocytes stimulated with phyto- haemagglutinin. The active supernatants from cul- tures of lymphocytes between 24 and 48 hours after stimulation with phytohaemagglutinin induced a significant increase in the collagen content and col- lagen synthesis rate of L929 fibroblasts. Fibrogenesis enhancing factor (FEF) in active supernatant is 56~ heat labile, loses its activity by the treatment of neuraminidase and trypsin and has a m.w. around

80,000. FEF was present in active supernatant from cultures of liver-specific-antigen-stimulated lyrnpho- cytes in 3 of 13 patients with chronic inactive hepati- tis and in 8 of 11 patients with chronic active hepati- tis. FEF could not demonstrate in active supernatant from cultures of HBsAg-stimulated lymphocytes both in 5 HBsAg healthy carriers and in 8 HBsAg positive chronic active hepatitis. These findings sug- gest that lymphocyte-mediated immunity play a key role in progression of hepatic fibrosis of the patients with chronic active hepatitis.

404 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

S y m p o s i u m (2):

Compl i ca t ions of L i v e r C i r rhos i s in Spec ia l Reference to the Pathophysio logy and Treatment of the Complications E x c l u d i n g M a l i g n a n c y :

Co-Modera tors : Dr. Kiyoshi I N O G U C H I and Dr. Sukeo Y A M A M O T O

Postoperative complications in severely cirrhotic patients

The Second Department of Internal Medicine, Kurume University School of Medicine

Takashi YOKOTA and Masahiro FUJII* The First Department @Surgery, Kyoto

University Medical School *The First Department of Internal Medicine,

Kyoto University Medical School

We investigated postoperative complications and alternations of the reticuloendothelial functions after liver surgery in patients with 50 cirrhotic, 13 noncirrhotic portal hypertentions and 72 hepatic tumors.

1) The colloidal gold clearance by Kupffer cells was remarkably reduced and that by spleen was in- creased in the cirrhotic patients. After splenectomy or hepatic resection, systemic dysfunction of the re- ticuloendothelial system occurred in the severely cir- rhotic patients.

2) After splenectomy or hepatic resection in these patients, specific complications such as remit- tent fever, endotoxemia, sepsis, respiratory failure, clotting abnormalities and gastrointestinal bleeding were not rarely observed and hepatic dysfunction often progressed secondarily. Moreover, the inter- vals of the intermittent fever and reduction of the clearance by Kupffer cells correlated with mortality rate.

These results indicates that the postoperative fea- tures in cirrhotic patients may be concerned with not only hepatocellular functions but phagocytic ac- tivities by Kupffer cells.

Endotoxemia in liver cirrhosis: correlation between endotoxemia and complications of

liver cirrhosis, specifically ascites and hemorrhage of the upper gastro-

intestinal tract

Hirohiko ABE and Atsushi TOYONAGA

1) Endotoxemia was found in 43% of 109 patients with liver cirrhosis and 50% of 70 patients with hepatoma and liver cirrhosis. 2) Patients with ascites showed high frequency of endotoxemia. 3) Ascites did not resolve in patients with endotoxin positive ascites. 4) Similarly, ascites did not resolve in pa- tients with persisting endotoxemia. 5) High fre- quency of SBP was found in patients with endotoxin positive ascites. 6) All patients with persisting endo- toxemia experienced episodes of hemorrhage from the upper GI tract, in contrast to only 27% of pa- tients without endotoxemia who experienced such episodes. 7) Patients with endotoxemia frequently demonstrated upper gastrointestinal lesions, par- ticularly erosions and peptic ulcers. 8) Thirty-seven percent of patients with liver cirrhosis showed re- solution of endotoxemia after the administration of lactulose. 2) Forty-five percent of patients treated with Polymixin B showed resolution of endotoxe-

mia.

Pathophysiology and surgical treatment of ascites accompanied by liver cirrhosis

Koro SAKODA and Takuro KAWADA The Second Department of Surgery, Kagoshima

University School of Medicine

Pathogenesis of ascites accompanied by liver cir- rhosis and its surgical treatment are studied in this paper. As experimental animals, mongrel dogs were

used and divided into three groups. Group I: con- sisted of normal dogs. Group II: consisted of the dogs with constriction of supradiaphragrnatic in- ferior vena cava (McKee's procedure). Group III: consisted of the dogs with splenopneumopexy and McKee's procedure. Clinically, the patients with

August 1981 Proceedings of 22nd Autumn Meeting 405

liver cirrhosis were studied from the aspects of pa- thogenesis and surgical treatment of ascites. Experi- mentally, wedged hepatic venous pressure (W.H.V.P.), portal pressure (P.P.), and post-

sinusoidal vascular resistance (P.V.R.) increased re- markably due to McKee's procedure. Thoracic duct lymph flow increased to 26 times of control value and plasma aldosterone increased continously in Group II. These changes obtained experimentally, could be observed in the patients with liver cirrhosis. As surgical treatment for ascites, portopulmonary shunt by splenopneumopexy was developed on the

basis of extensive study of hepatopneumopexy. By

this portopulmonary shunt, W.H.V.P., P.P., and

P.V.R., elevated due to McKee's procedure, were alleviated remarkably. Consequently, increased

thoracic duct lymph flow and hyperaldosteronism caused by McKee's procedure, was significantly al- leviated by this shunt. Thus, ascites was well con- trolled. This procedure was performed on nine cir- rhotic patients with ascites. Postoperatively recur-

rent ascites could not be observed in all cases but one of operative death. Peritoneovenous shunt by LeVeen was proved to be an effective procedure to control ascites in liver cirrhosis and experimental ascites. However, it is very important to keep in mind that peritoneovenous shunt of ascites is very

susceptible to disseminated intravascular coagulo-

pathy.

Reference

1) Akita H, Sakoda K: Portopulmonary shunt by

splenopneumopexy as a surgical treatment of Budd-Chiari syndrome. Surgery 87: 85-94, 1980

Pathophysiology and intervention of hepatic encephalopathy with special reference

to amino acid imbalance

Yasuhiko KAWADE and Yasutoshi MUTO

The First Department of lnternal Medicine, Gifu University School of Medicine, Gifu

As compared with the absence of hepatic en- cephalopathy, significant reduction in plasma BCAA; branched chain amino acid levels, Fischer's ratio (BCAA to AAA; aromatic amino acid ratio)

and elevation in plasma ammonia concentration were observed in the presence of hepatic encephalo- pathy due to liver cirrhosis. A study on femoral

arterio-venous difference of amino acid in whole

blood revealed significant positive correlation be- tween arterial ammonia level and net balance of

BCAA, suggesting that hyperammonemia is respon- sible for increased oxidation of BCAA, in order to

detoxify ammonia through glutamine synthesis in

the skeletal muscle. Ammonia as well as short chain fatty acid are assumed to enhance decarboxylation of alpha-oxo-BCAA that is a rate-limiting step. In fact, parenteral administration of 0.2 M ammonium acetate or 0.08M caproic acid into normal rats (4 ml/hr, for 24 hr) brought about significant reduc- tion in plasma BCAA level. Moreover, the adminis- tration of ammonia induced significant increases of both AAA and serotonin levels in the brain, which were restored toward normal after administration of BCAA solution.

Long-term supplementation with BCAA granules (0.3g/kg, for 3 months) in patients with decompen- sated liver cirrhosis, who had episodes of encephalo-

pathy, was found to prevent the development of

hepatic coma. Furthermore, the supplementation

also brought about significant elevation of serum albumin level (from 2.9 _ 0.4 to 3.4 + 0.5 g/dl), de- spite shortened biological half life of 125I-RISA.

In conclusion, these results strongly suggest that amino acid imbalance, particularly relative and/or absolute deficiency of BCAA, plays an important role in development of hepatic encephalopathy as well as in disordered protein metabolism (i.e., albu- min synthesis in the liver).

Hepatic encephalpathy--Its pathogenesis and treatment

Akira OKADA and Shinkichi KAMATA

The First Department of Surgery, Osaka University Medical School

There is a growing trend to metabolic and nutri- tional control of hepatic encephalopathy (HE). In an attempt to control HE by tailoring amino acid pattern in the hyperalimentation fluid, we formu- lated a new amino acid mixture. Since 1975, we

406 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

have treated 20 cases of HE with this regimen. Six-

teen of them showed marked improvement of con-

sciousness soon after this amino acid mixture was in-

jected. To clarify the mechanism of the clinical

effects, an experimental study was performed. We

examined the effects, an experimental study was

performed. We examined the effects of dietary aro-

matic amino acids and branched chain amino acids

on brain amine metabolism in rats with a portocaval

shunt. These rats were fed several kinds of diet con-

taining different amino acid compositions. These

results and its relation to the behavioral changes of

experimental animals are discussed.

Postoperative complications of cirrhotic patients and beneficial effects of trans

portal insulin supplementation

There are many postoperative problems in pa-

tients with liver cirrhosis resulting in high mortality.

It is supposed to be due to decrease of functioning

liver cell mass and metabolic disturbances of the cir-

rhotic liver. Blood glucose, insulin, immunoreactive

connecting peptide (CPR) and glucagon (IRG)

levels in the portal blood were compared with those

of systemic blood after intravenous administration

in patients with and without cirrhosis. Intravenous

NHs tolerance tests were also performed in cirrhotic

patients. According to the above study, it was postu-

lated that transportal insulin supplementation (TPI

treatment) was beneficial for cirrhotic patients. TPI

t reatment performed postoperatively in cirrhotic

patients, and effects of the treatment on liver func-

tion were studied by various methods.

Conclusion: 1) Cirrhotic patients have glucose in-

tolerance because of relative hyposecretion of endo-

genous insulin and hypersecretion of glucagon. 2)

Cirrhotic patients are in long-standing catabolic

states, e.g., gluconeogenesis and glycogenolysis. 3)

TPI treatment enhances endogenous insulin release

after glucose administration for cirrhotic patients.

4) GOT and GPT levels and ICG Rmax were

markedly improved by T P I in patients with cirrhosis

and active hepatitis. 5) Serum aminograms,

B C A A / A A A were not effected by TPI treatment. 6)

Two of three chronic aggressive hepatitis patients

were recovered to inactive type by TPI treatment,

verified by light and electron microscope. 7) TPI

treatment is beneficial for cirrhotic patients by its

three major effects, hepatotrophic effects, improve-

ment of metabolic disorder and impaired liver func-

tion.

The study of the pathogenesis of gastric mucosal lesion in liver cirrhosis

Teisuke KAMATA and Kenzo KOBAYASHI

The Third Department of lnternal Medicine, Osaka City University Medical School

In patients with liver cirrhosis, gastric mucosal

lesions accompanied with severe bleeding were oc-

cured frequently, so, in order to make clear their

pathogenesis, experimental studies in rats with car-

bon tetrachloride-induced liver damage were per-

formed. The results obtained were summarized as

follows: 1) Gastric acid secretion: Basal acid secretion

and augumentative stimulated secretion were ele-

vated in rats with hepatic damage, compared with

control rats.

2) The back diffusion of luminal hydrogen ions

into the gastric mucosa (H + back diffusion): The en-

hancement of H+ back diffusion were observed in

rats with hepatic damage.

3) Prostaglandin E: The prostaglandin E in the

gastric mucosa at pyloric and fundic regions were

more decreased in rats with hepatic damage than in

control.

4) In rats with hepatic damage, the histological

findings of the gastric mucosa were as follows: The

length of the gastric foveolae were shortened short,

but that of the gastric gland were elongated. The

number of the parietal cell was increased, but that

of the mucous neck cell was decreased.

These above mentioned findings seemed to show

functionally and histologically that in chronic hepa-

tic damage, the offensive factor against gastric

mucosa increased, on the other hand, the defensive

factor in gastric mucosa decreased. The more severe

the hepatic damage, the weaker the defensive

August 1981 Proceedings of 22nd Autumn Meeting 407

factor.

It seemed to lead to the speculation that they

might play important roles in production of the gas-

tric mucosal lesions in liver cirrhosis.

Gastroduodenal lesions in c i r rhot ic portal

hypertension "pathogenesis and surgical treatment"

Yoshinori INAGAKI and Teruaki AOKI

The Second Department of Surgery, Jikei University School of Medicine

During last 5 years, 130 cirrhotic portal hyperten-

sion with esophageal varices were surgically treated

by so called direct procedures, including transab-

dominal esophageal transection, devascularization

of esophagus and upper part of stomach, splenec-

tomy soon.

Among these 130 cases, as causes of bleeding,

28.6 % of gastroduodenal lesions have been encoun-

tered, although the rate of gastroduodenal lesions

including 63 % of gastric varices, 58.5 % of erosions,

35.6% of gastroduodenal ulcers were documented.

Those gastric lesions except duodenal ulcer were

found mainly in the area of upper part of stomach

associated with severe intestinal metaplasia, glandu-

lar atrophy congestion of capillaries intra mucosal

bleeding, inflammatory cell infiltration and sub-

mucosal changes of dilated and sclerotic vessels, all

of which are pertinent with circulatory disturbances

of the area.

Acid secretory test and gastrin determination sug-

gested a little influences, on these lesions, except

duodenal ulcers if any. Based on these findings,

treatments of combined gastric lesions with esoph-

ageal varices must be considered. Carefully, and so

far vagotomy plus proximal gastrectomy with ad-

equate pyloroplasty have given satisfactory results.

On the other hand, duodenal ulcers have been well

treated by vagotomy plus drainage procedures,

which rather easily performed concomitant with

transabdominal transection of the esophagus.

Cl inical studies of portaI hypertension and obliteration of esophageal varices

by percutaneous t ranshepat ic

catheterization of the portal vein

Kenichi TAKAYASU and Hirotaka MUSHA*

*The First Department of Medicine, Chiba University School of Medicine

(Chief Director: Prof. gunio OKUDA)

Percutaneous transhepatic portography was per-

formed in 211 patients with various hepatic diseases.

In 150 cases the new method using a "sheath"

catheter and PTC needle was performed. After the

development of this new method, the success rate

was improved from 59.0% to extrahepatic col-

laterals were analysed in the portograms and the

results indicated that collaterals most frequently in-

volved the vessels supplying blood to esophageal

varices (the left gastric and short gastric veins) in

various hepatic diseases with portal hypertension.

The degree of extrahepatic shunt index (EHSI) was

also measured using radiolabelled macroaggregated

albumin in 28 cases. EHSI was correlated with the

degree of opacification of the left gastric vein. Pa-

tients with a high EHSI tended to have or have had

hematemesis, and 80% of patients with hemateme-

sis showed an EHSI more than 35% and portal vein

pressure more than 360 mm H~O. These two para-

meters were thought to be very useful in deciding on

an elective operation and in percutaneous trans-

hepatic obliteration (PTO). PTO was performed in

26 patients, 29 times, using stainless steel coils, a

balloon catheter and gelfoam, etc. Except for one

patient, obliteration was successful in all and

hematemesis was stopped.

Pre- and postoperative hypoxemia and in-

creased postoperative pulmonary complicat ions in patients wi th

liver cirrhosis

Takero YOSHIDA and Kiyoshi INOKUCHI

The Second Department of Surgery, Kyushu University School of Medicine

Hypoxemia and hyperventilation in patients with

liver cirrhosis has not been fully explained. A more

severe postoperative hypoxemia and a higher inci-

dence of postoperative pulmonary complications

408 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

were found in patients with liver cirrhosis compared

to patients without liver cirrhosis in this series. To

clarify the cause of such pre- and postoperative

hypoxemia, pulmonary function was studied. Vital capacity, forced expiratory volume in one

second, total lung capacity and residual volume were within normal values. The flow volume curve

and closing volume, however, were abnormal in the

majority. The maximal expiratory flow at 25 per- cent of forced vital capacity ('~25) was significantly

decreased and the closing volume was significantly

increased. Pulmonary true shunt was not increased

as shown by the pure oxygen breathing test either

before or after operation.

It is concluded that pre- and postoperative hypo- xemia may partly depend on the compression of small airways in the dependent lung zone with a resulting decrease in the "v'A/Q ratio. An increased incidence of postoperative pulmonary complications may also be due to easily collapsible small airways.

References

1) Ruff F, et al: Regional lung function in patients

with hepatic cirrhosis. J Clin Invest 50: 2403, 1971

2) Yoshida T, et al: Evaluation of the risk of post-

operative pulmonary complications. Jpn J Surg 7: 131, 1977

August 1981 Proceedings of 22nd Autumn Meeting 409

Symposium (3):

Upper Gastrointestinal Bleeding--Special Device and Procedure to Stop Hemorrhage: Co-Moderators: Dr. Fusahiro NAGAO and Dr. Masayoshi NAMIKI

Endoscopic diagnosis and control of bleeding esophageal varices with a translucent

balloon tamponade tube

Yasuo IDEZUKI

Department of Surgery, St. Marianna University School of Medicine, 2095 Sugao,

Takatsu-ku, Kawasaki, Japan 213

Successful control of bleeding esophageal varices

by esophagogastric balloon tamponade is life-saving and is an initial step for emergency or elective sur- gery. Sengstaken-Blakemore's tripple lumen double balloon tube (S-B tube) is widely used but it is some- times ineffective because of improper positioning of the balloon or insufficient compression of varices. Also, erosion, pressure necrosis, ulceration, and

denudation of esophageal mucosa due to over-com- pression by the balloon have been reported. In order

to prevent these shortcomings of the current balloon tamponade, we have modified S-B tube so that the

diagnosis and control of bleeding varices could be made under the direct vision by fiberoptic esophago- scopy. Essential structure of the modified tube is

similar to that of S-B tube. Main modifications are; 1) internal diameter of the core tube is enlarged to

8 mm so that a thin fiberoptic endoscope (less than 6 mm in diameter) can be inserted into the lumen of the tube, 2) both the core tube and the esophageal ballon are made of translucent polymers so that the endoscopic observation of the esophagus is possible from the lumen of the core tube. This endoscopic tampounde tube was used in 41 patients for 61 occa- sions of variceal bleeding. Diagnosis and localization of ruptured varices were easily made by an endo- scope passed into the tube. Bleeding was successfuly stopped in 59 occasions by inflating the esophageal balloon with the pressure of 16-42 mmHg. (Average 29.6 mmHg) with our new transparent tamponade

tube. Endoscopic diagnosis and control of bleeding could be safely made, and most of the failures and

complications inherent to S-B tube could be avoided

since the process of compression of varices is con- stantly observable.

Continuous intravenous infusion of pitressin in hemorrhage from esophageal varices

Jiroichi ONO and Koro SAKODA The Second Department of Surgery, Kagoshima

University School of Medicine

Vasopressin was reported by Kehne in 1956 to be useful in the treatment of bleeding esophageal varices. During the succeeding 20 year, controlled clinical trials have shown that pitressin is effective in controlling hemorrhage from esophageal varices. A controlled comparison of continuous intravenous in-

fusion of pitressin (IVP) and Patton (S-B) tube in

hemorrhage from esophageal varices was under- taken. Thirty four cirrhotic patients were evaluated

during a five year period. Of these patients, 22 were

received IVP and 12 were treated with Patton tube. The success in controlling hemorrhage were 82 % in IVP compared with 14% in Patton tube. The re- quirement of blood transfusion, of which amount was 2,700 ml in IVP, was significantly reduced in comparison of 5,100ml in Patton tube. Average duration of IVP was 8.6 days. IVP was aperformed 0.1 u /min on this study with closed observation of these patients maintaining the level of 100 in systolic blood pressure and 25 in Hct.

In conclusion, it is recommended that IVP, which can be administered easily and safe, is given a brief therapeutic trial early in the management of hemor- rhage from esophageal varices. Elective surgery should be done thereafter.

Endoscopic embolization of bleeding esophageal varices

Yasuhiro TAKASE and Takao SAKITA Department of Gastroenterology, Institute

of Clinical Medical Science, University of Tsukuba

410 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

In our institute, hemostasis by endoscopic emboli-

zation has been already performed in 21 patients of

esophageal varices. Hemostasis was successful in 20

of 21 patients of bleeding esophageal varices. The

injecting drug we are using now is 5% ethanolamine

oleate.

The advantage of endoscopic embolization in

hemostasis of bleeding esophageal varices are: 1)

This method can be performed in the same proce-

dure as the endoscopy for the upper gastrointestinal

tract. 2) This method is simple in technique. 3) This

method can be performed steadily and safely by con-

firming the location of the needle fluoroscopically

after it is punctured into esophageal varix. 4) By this

method, not only the injected varix but also ad-

jacent ones can be embolized one after another. 5)

The esophageal varix once embolized has no re-

bleeding. 6) The repeated embolization of esoph-

ageal varix persisting after emergent hemostasis can

prevent variceal bleeding for at least 12 months.

T h e angiographic therapeut ic appl icat ion

of massive gastrointest inal

b leed ing

Shoichi KUSANO* and Sumio MATAMA**

Departments of Radiology * and Internal Medicine **, Kitasato University Hospital,

1-15-1, Kitasato, Sagamihara, Kanagawa, Japan

Fifty-nine patients with massive gastrointestinal

bleeding treated angiographically during the six-

year period from 1974 to 1980 were analyzed and

discussed. When angiography demonstrated the extravasa-

tion of contrast medium immediately after the injec-

tion from the bleeding ulcer of the upper gastro-

intestinal tract, it was actually useful in determining

whether the ulcer was of superficial or deep type.

The extravasation from the ulcer of superficial type

was always demonstrated from the periphery of the

arterial branch after passing through the subserosal

layer, in stomach within the zone about 2 cm inward

from the lesser or greater curvature. The extravasa-

tion from the ulcer of deep type was visualized

directly from the major branch running in the sub-

serosal layer or extraserosally.

Depending on this new angiographic criteria, we

tried to evaluate 12 patients with bleeding ulcers of

the gastrointestinal tract. In this series, 10 with ac-

tive bleeding from a superficial ulcer were all

treated successfully with either vasopressin infusion

or transcatheter embolization with ethyl 2-cyano-

acrylate (Alonalpha-A). 6 out of these 10 patients

needed neither surgical intervention nor blood

transfusson in a large amount and 4 were followed

by urgent operation after the angiographic success-

ful control. Therefore the authors think that surgery

for the patients with active bleeding from a superfi-

cial ulcer should be done electively. In contrast to

this good results, 2 patients with massive bleeding

from a deep ulcer were uncountrolled in spite of the

fact that transcatheter embolization was completely

performed. Then surgical intervention after angio-

graphic treatment should be immediately planned.

-For these patients, combined therapy with trans-

catheter embolization and endoscopic laser coagula-

tion is expected to be widely used in the near future

to avoid emergency operation which often causes

severe complications. Because transcatheter emboli-

zation has a possibility of causing infraction of the

upper abdominal organs, it should be indicated only

for the patients in whom vasopressin infusion has

failed to control the bleeding and for the patients

with active bleeding from duodenal ulcer, penetrat-

ing ulcer and malignant neoplasm, of which the suc-

cess rate with vasopressin infusion is generally low.

Six patients with massive bleeding from the gas-

trointestinal malignant neoplasms were also treated

with transcatheter embolization with Alonalpha-A.

In this group, 4 with carcinoma of relatively

localized type, the so-called Borrman type III, were

so successfully controlled that only a very small

amount of blood was needed for transfuufusion.

However, the remaining 2 with malignancies of

diffusely spreading and multiple types rebeled after

transcatheter embolization and needed blood trans-

fusion in a large amount up to death.

Thirty-four patients with massive gastroesoph-

ageal variceal bleeding were treated with vasopres-

sin infusion nrom the superior mesenteric artery

(VI) and /or with pereutaneous transhepatic ob-

literation of the gastric veins (PTO). In contrast to

the low success rate of 48% only by the conservative

August 1981 Proceedings of 22nd Autumn Meeting 411

standard measures, using VI and PTO we obtained

the success rate of 81% and 94%, respectively. Re-

garding the duration of controlling the bleeding

from the gastroesophageal varices, VI was less suc-

cessful than PTO, although the technique of the

former was simpler and easier than that of the

latter. The indications and complications of these angio-

graphic treatments were discussed and several ex-

amples were presented.

Transcatheter embolization for control of massive upper GI bleeding

Joe ARIYAMA

Department of Gastroenterology, Juntendo University, Tokyo, Japan

Indications for transcatheter embolization have

been defined as follows: (I) patient with massive

upper GI bleeding where hemostasis is not possible

with medical therapy; (2) high risk patient for emer-

gency operation. Twenty patients with massive arte-

rial bleeding from upper GI tract were treated with

transcatheter embolization. These include 12 gastric

ulcers, 3 duodenal ulcers, 4 gastric cancer and one

pancreatic carcinoma. Permanent control of bleed-

ing was achieved in 14 patients. Fifteen patients with

esophageal varices were treated by percutaneous

transhepatic obliteration. In 6 acute bleeders hemo-

stasis was successful in 5. After the obliteration of

the varices recanalization was frequently observed

by left gastric antiography. This procedure will not

improve the prognosis of patient with esophageal

varices. However, this procedure is effective for

acute bleeder to stop bleeding and elective operation

can be performed safely.

Percutaneous transhepatic obliteration of gastroesophageal varices; utilization

of ultrasonically-guided portal-vein puncture

Kunio KIMURA and Masao O H T O

The First Department of Medicine, Chiba University School of Medicine,

Chiba, Japan

Effectiveness of percutaneous transhepatic ob-

literation of gastroesophageal varices (PTO) and

usefulness of ultrasonically-guided percutaneous

transhepatic portography (PTP) were discussed.

On 85 patients with gastroesphageal varices 118

PTO were carried out. Successful hemostasis was ob-

tained in 52 (91.2%) out of 57 performances on

active bleeders. Complete embolization of opacified

variceal supplies was made in 70% of all the per-

formances. Improvement of endoscopic findings of

the varices was recognized; the size was diminished

in 71%, and the red-color sign was reduced or dis-

appeared in 91%.

PTP was done by means of ultrasonic guidance on

82 performances and X-ray control using a thin

needle on 36. Ultrasonically-guided PTO was suc-

cessfully performed without any complication on 13

patients with focal liver diseases, 11 hepatomas, 1

hemangioma, and 1 hepatolithiasis. By use of ultra-

sonic guidance, suitable .portal-vein-branch was

safely and accurately punctured with minimal num-

ber of puncture attempts (average, 1.3). Therefore,

the method was possible to perform on patients with

massive ascites (28 performances). Puncture of the

left portal-vein-branch from the anterior abdominal

wall was required in 3 patients with hepatoma and 1

with markedly shrunk right lobe of the liver.

Hemostatic procedure by endoscopic local injection of HS-E solution, with

special reference to changes of blood flow in the tissue

Masanori HIRAO* and Takashi KOBAYASHI* *

�9 Department of Surgery, Chuo Hospital, Hokkaido Association of Medical

Service for Workers, Sapporo �9 *Department of Internal Medicine, do

We have recently developed a new method of

endoscopic local injection of hypertonic sodium epi-

nephrine (HS-E) solution to arrest hemorrhage from

the upper digestive tract.

As a fundamental experiment, we made a re-

search to check hemostatic effect from the viewpoint

of changes of blood flow in the tissue where local

injection of HS-E was applied. HS-E solution of vari-

412 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

ous concentration was locally injected into the gas-

tric wall of Wistar strain rats. Submucosa of ante-

rior gastric body was chosen as injection site. Blood flow in the tissue following injection was measured with hydrogen gas method. In our experimental design, rats were divided into three groups. Group I; controls, Group II; those applied local injection of 0.2ml of HS-E (16 x 2), with sodium 155 mEq/L and epinephrine 0.05 mg/ml, Group III; those ap- plied local injection of 0.2ml of HS-E (4 x 2), with sodium 625 mEq/L and epinephrine 0.05 mg/ml. Significant reduction of blood flow was observed in both group II and group III compared with group I at one hour after HS-E injection (p<0.001). By two hours after HS-E injection, however, blood flow re-

covered so well in group II that no significant differ- ence in blood flow was detected between group I and

group II. In group III, up to nine hours after injec- tion, blood flow reduction was significantly greater than in controls (p<0.05). Histological changes in the gastric wall brought about by local injection of

HS-E included such pathological features as fibri- noid degeneration of arterial walls and thrombus formation. These pathohistological changes are

consistent with and can be explained by functional changes of blood flow in the tissue.

On the basis of the above mentioned results, we applied the hemostatic method to clinical cases. Be- tween October 1978 and September 1980, thirty- four cases underwent endoscopic local injection of HS-E to arrest hemorrhage from the japper digestive tract. Patients were 29 males and 5 females from 23 to 75 in age with a mean of 61. Thirty-four cases consisted of gastric ulcer (20), duodenal ulcer (3), stomal ulcer (4), Mallory-Weiss syndrome (2) and

others (5). Serious concomitant diseases were ob- served in about 70% of all cases at time of hemor- rhage. Types of bleeding were arterial (13), oozing (15) and blood coagula forming (6). Exposed ar-

teries were observed in 24 cases (70.6%). Clinical effectiveness was obtained in 32 cases (94.1%),

where permanent and temporary arrest of hemor- rhage were demonstrated in 28 (82.3%) and in 4 cases (11.8%), respectively. For the purpose of pre- venting re-bleeding after initial arrest of hemor- rhage in emergency, a couple of further injection at

intervals of 24 hours were performed with benefit. Likewise, when the exposed artery was not bleeding yet, prophylactic injection of HS-E was undertaken in the same manner to prevent impending hemor- rhage. These prophylactic measures have hitherto been helpful.

Reasonable therapeutical procedure for the stress ulcer with hemorrhage. --Clinical evaluation of gastrin

receptor antagonist and H2 receptor antagonistm

Masaki KITAJIMA and Satoru SOHMA Department of Surgery, Kyorin University

Severe stress in the form of major surgery, trauma or thermal enjury is frequently followed by the de- velopment of stress ulcer. Several explanations about the pathogenesis of this phenomenon have been reported and recently the attention has been focused on the disruption of the defence mechanism of the gastric mucosa, such as impaired mucus pro- duction~), gastric acid hypersecretion 2) and abnor-

mal permeability of gastric mucosa to hydrogen

ions s,4) that may possibily be related to local

mucosal ischemiaS). So far we have investigated that gastrin receptor antagonist proglumide and H2-

receptor antagonist cimetidine were proved to de- crease hypersecretion and to strengthen the mucosal

defence mechanism. On the basis of these experi- mental data, the clinical efficacy of the proglumide and cimetidine were studied. Sixteen patients with active gastric bleeding as well as for 8 patients under high risk of bleeding were managed with proglu- mide and 11 patients with bleeding were also treated with cimetidine. Bleeding condition was assessed by endoscopy and clinical signs. Proglumide was given as a suspension of 800 mg/dl of saline by intragastric tube, 4 times daily, and cimetidine was also ad- ministered 200 mg/dl of saline. Only 5 patients in

proglumide group and 2 in cimetidine group had to

be referred for urgent surgery. Clinical and biologi-

cal tolerance were excellent. Among 42 bleeding pa- tients treated with ice-cold saline plus thrombin gas-

tric irrigation, 19 had be referred for urgent surgery and 4 actually died from active bleeding. In no case

August 1981 Proceedings of 22nd Autumn Meeting 413

did massive life--threatening gastrointestinal bleed-

ing developed after proglumide and cimetidine

treatment.

References

1) O'Neill JA Jr, et al: Influence of thermal burns on gastric mucus production. 17: 293, 1966

2) Poter RW, et al: Hypothalamic influences on hydrochloric acid secretion of stomach. Surgery 33: 875, 1953

3) Kitajima M, et al: Gastric mucosal lesions after burn injury relationship to H + back diffusion

and the microcirculation. J Trauma 18: 644,

1978 4) Kitajima M, et al: The experimental studies on

stress ulcer of the stomach following thermal in- jury with special reference to H § back diffusion

and microcirculation. Gastroenterol Jpn 13: 175, 1978

5) Kitajima M, et al: Gastric mucosal blood flow

and mucosal permeability changes in burns. In: Defence Mechanism of the Gastrointestinal Mucosa. Proceedings of the Symposium held in Kyoto, Feb 15-16. K Kawai Ed, P 43

Emergency treatment of upper gastro- intestinal hemorrhages with medical

vagotomy and cimetidine

Mitsugi SUGIYAMA and Shuji TSUCHIYA The Second Department of Surgery, Yokohama

City University School of Medicine

We have reported the results of comparative study between cimetidine therapy and medical vatotomy in the treatment of the emergency cases of upper

gastrointestinal bleeding. As a prophylactic treat-

ment cooled antacids solution (Maalox, etc.) were frequently introduced into the stomach by a naso-

gastric tube and by way of medical vagotomy with intermittent administration of hexamethonium bro- mide (C6: 25-50mg) and atropine sulfate (0.5 rag). The cimetidine therapy was conducted by adminis- tration intravenously 200 mg every 6 hours.

1. Emergency hemostatic effect: With the medi- cal vagotomy treatment; from 60 cases, 20 remark- ably effective, 13 effective, 27 ineffective. With the

cimetidine therapy; from 30 cases, remarkably

effective 13, effective 15, ineffective 5. 2. Hemostatic effect and lesions: Although the

medical vagotomy was markedly effective in 42.8% of the cases with slight erosion (UI I-II), in the case

of deeper lesion of U1 III-IV, it was only markedly

effective in 3 out of 7 cases in which deeper had ex- posed the blood vessels. 5 cases of 20 markedly effec-

�9 rive to the medical vagotomy, 10 cases of 13 effective and 15 cases of 27 ineffective were finally operated

sometime after. Seven out of 30 cases were died post- operatively. Under cimetidine therapy, 7 cases were

operable and there was no mortality cases. However, even after the hemostasis there was an unfavorable prognosis in that 16 cases died of the primary dis-

ease.

References

1) Barry A Levine, et al: The role of cimetidine in the prevention of stress induced gastric mucosal injury. SGO 148: 399-402, 1979

2) Gillespie IE, et al: Effect of medical and surgical vagotomy on the augmented histamine test in man. Brit MedJ 1: 1557, 1961

3) Sugiyama M: Operative indication for peptic

ulcer by lont-term results. The Japanese Journal of Practionaly Surgery 40(3): 54-60, 1979

4) Sugiyama M, et al: Pathophysiology and treat-

ment of acute gastric mucosal lesion and acute

gastric ulcer. Jpn J Gastroenterol Surg 12(7): 417-424, 1979

A fundamental experiment on laser photocoagulation

Toshiro KONISHI and Yuji MARUYAMA The Second Department of Surgery, Faculty

of Medicine, University of Tokyo

Endoscopic laser irradiation is finding worldwide acceptance as a new useful therapeutic method for gastrointestinal bleeding. We conducted animal ex- periments to investigate the safety and effectiveness

of the irradiation of both Nd-YAG and argon lasers which are now available for the clinical use of endo-

scopic laser photocoagulation. We also compared the effectiveness of laser irradiation and electro-

414 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

coagulation in the arresting of bleeding from gastric

ulcers.

1. Twenty to 50 watt Nd-YAG laser and 3 to 8

watt argon laser were irradiated on the gastric

mucosa of 8 mongrel dogs for 2 to 10 seconds. A his-

tological examination disclosed that Nd-YAG ir-

radiation could shrink the submucosal tissue more

thickly and markedly, and might be useful for

hemostasis. The irradiation of high power argon

laser is claimed to be safe from perforation because

the blue-green light is absorbed near the mucosal

surface by blood. However, high power argon laser

perforated the whole thickness of the gastric wall in

a short time. Argon laser irradiation to the alimen-

tary tract was thus demonstrated to be not always

safe.

2. Fifty watt Nd-YAG laser was irradiated on

the gastric mucosa of 5 mongrel dogs at a distance of

1 cm for 3 to 10 seconds. The stomach was extir-

pated and investigated histologically by the H-E

stains 1, 2, 3, 4 and 6 weeks after irradiation. All

gastric ulcers made by laser irradiation were almost

spontaneously healed and reepithelized after 3

weeks.

3. Bleeding from gastric ulcers produced by an

ulcer maker in 8 heparinized mongrel dogs.was ar-

rested by Nd-YAG and argon laser irradiation and

electrocoagulation. However, complete hemostasis

was achieved more rapidly by Nd-YAG laser than by

argon laser and electrocoagulation.

References

1) Konishi T, et al: Gastroenterol Endosc 22:

442-449, 1980

2) Kiefhaber P, et al: Prog Surg 15: 140-155, 1977

3) Frumorgen P, et al: Gastroenterol Endosc 21:

243-246, 1979

4) Mizushima T, et al: Gastroenterol Endosc 21:

1289-1295, 1979

Hemostasis of upper gastro-intestinal hemorrhage by laser endoscopy

mClinical evaluation of Nd-YAG laser and Argon lasern

Yoshito OHSHITA and Shigemi ARIYAMA

The First Division, Department of lnternal

Medicine, Yamaguchi University School of Medicine

Clinical evaluation of hemostasis of upper gastro-

intestinal hemorrhage by endoscopic laser photo-

coagulation performed in 30 cases is discussed.

Twenty-one of the 30 cases were photocoagulated

by Nd-YAG laser, including 4 Mallory-Weiss syn-

drome cases, 8 gastric ulcers, 1 duodenal ulcer, 1

stomal ulcer, 1 gastric polyp, 2 gastric carcinomas

and. 4 cases of bleeding after polypectomy. Of these,

hemostasis was successful in 18 cases (86 %). Severity

was classified by Nagao's classification. There were 5

severe cases and of these, the bleeding could not be

stopped in three cases during the early period of this

study because of insufficient coagulation. The bleed-

ing in all moderate and slight cases could be

stopped.

Nine of the 30 cases were photocoagulated by

Argon laser, including 4 gastric ulcers, 2 duodenal

ulcers, 1 esophageal erosion and 2 gastric carcino-

mas. Of these, hemostasis was successful in 6 cases

(67 %). The remaining 3 cases were severe cases with

exposed blood vessels, and the bleeding could not be

stopped even though in 2 cases there was sufficient

irradiation.

The evaluation of these results reveals that laser

photocoagulation is effective to stop upper gastro-

intestinal bleeding. But the hemostatic effect of Nd-

YAG laser is better than that of the argon laser. The

argon laser is not satisfactory for massive hemor-

rhage. The cooperation of an anesthetist is needed

to stop severe hemorrhage under general anesthesia.

Endoscopic laser coagulation of gastro- intestinal bleeding

K. H A R A D A and K. MIZUSHIMA

The Third Department of Internal Medicine, Asahikawa Medical College

We have had studies of the use of YAG laser to

treat the G.I .T. bleeding in clinically and experi-

mentally.

The lesions were bleeding gastric ulcer, stress

ulcer, bleeding gastric polyp, bleeding colon-polyp

and Osler's disease.

We have presented previously that the least out-

August 1981 Proceedings of 22nd Autumn Meeting 415

put of laser in treating the venous bleeding should

be 45 w and above. Now we have studied the his-

tologic changes of gastric wall by laser radiation and

temperature measuring simultaneously in dog ex-

periment. The out-put of YAG laser (Molection) was

60 w and the number radiation were 3 times in 3

seconds, the average temperature of the serosa

membrane was 59.4~ In 70 w and above, the his-

tologic changes showed that the muscular layer and

serosa membrane were necrosed. The region of

lesion was healed after 4 weeks and no perforation

was seen. The time of bleeding stop completely in

venous hemorrhage was 4.8 sec. in 60 w, 4.0 sec. in

70 w, 3.4 sec. in 80 w and 3.3 sec. in 90 w. Hence,

the suitable out-put was 60 w to 70 w. However,

there is not much satisfaction in treating the arterial

bleeding.

In order to attain more effective hemostatic, the

following methods are studied.

We have investigated the hemostatie procedure

which combined the photocoagulation by the laser-

coagulator with the endoscopic local injections of

the hypertonic sodium-epinephrin solution, in order

to attain more effective hemostasis on the hemor-

rhagic lesions of the stomach.

We are testing the guartz fiber which was specifi-

cally designed for the usage for the common lateral

view-type of endoscopy.

Notwithstanding, there is a limitation in laser

therapy. However, the emergency operation is

avoidable and reducible.

Emergent endoscopic laser therapy and endoscopic sclerosing therapy for upper gastrointest inal bleeding

Hiroaki SUZUKI and Yutaka W A T A N A B E

The Second Department of Surgery, Jikei

University School of Medicine, Tokyo

Recently, 17 cases of upper gastrointestinal bleed-

ing with hemorrhagic shock have been treated by

endoscopic laser therapy and 12 cases of bleeding

esophageal varices have been treated by endoacopic

sclerosing therapy in our department. The follow up

results of these therapies were reported in this pre-

sentation.

Nd-YAG laser syste m (MEDILAS, MBB) was used

for laser irradiation and tess than 15 shots with 60 or

70 w of irradiation power and 0.5 sec. of exposure

time were used for the treatment of a bleeding

lesion. A thin (12.6mm) LASER endoscope (FIT*

2T) was made by us with the help of Olympus. For

the endoscopic sclerosing therapy, 20ml of 1%

Aethoxysklerol (Kreussler) was injected paravasally

and intravasally through specially made polyethylen

tube with 23G needle. Such cases were followed up

with additional sclerosing therapies for more than 6

months.

The follow up results of these therapies are as fol-

lows:

1) After the laser therapy, more than 3 day hemo-

stasis could be obtained in 16 cases with an excep-

tional case of esophageal varices with serious bleed-

ing. Rebleeding occurred in 4 cases, 2 of them were

treated by emergent operation and 2 were treated by

repeat laser therapy or Sengstaken tube. 2) By the

sclerosing therapy, more than 6 day hemostasis

could be obtained in all the cases. Rebleeding oc-

curred in 4 cases, 2 of them died at home due to

massive bleeding and 2 were treated by emergent

operation or Sengstaken tube.

Conclusively, both endoscopic therapies were

found to be very effective to stop bleeding in cases of

upper gastrointestinal bleeding.

416 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

Symposium (4):

Indications for Endoscopic Polypectomy of the Stomach: C o - M o d e r a t o r s : Dr. Sa to ru S O M A a n d Dr. M a m o r u N I S H I Z A W A

Early diagnosis of cancer of the upper part of the stomach

Takashi IKEDA and Akio SHIRANE*

Sendai Medical Center, *Cancer Detection Center of Miyagi Cancer Society

Early diagnosis of the gastric cancer at the upper

part has been difficult. Practice of the diagnosis in

the gastric mass survey carried out by Miyagi Cancer

Society from 1974 to 1978 was studied. From this

study 43 cases of double cancer and 15 cases of un-

defined cancer were excluded. The availability of in-

direct X-ray examination is estimated mainly by the

frequency of the true lesion check. The availability

of endoscopic examination is estimated by the num-

ber of examination carried out until the final diag-

nosis. The frequency of C region check is extremely

low compared with other regions. As for the false

negative rate of indirect X-ray examination, that of

the C region is 30.6% and this is higher percentage

compared with those of the M region (20.0%) and A

region (13.9%). About the diagnostic process of

endoscopy, 87.5% cases of advanced cancer are

diagnosed by the first examination. On the other

hand only 25.0 % cases of early cancer are ~iagnosed

by the first examination. In order to diagnose gastric

cancer near the E-C junction, it is necessary to ex-

amine with U-turn and strong down angle method

by side-view endoscopy.

Radiologic detection of early cancer localized within 2 cm from esophago-cardia junction

Yasumasa BABA and Takeshi NINOMIYA

Department of lnternal Medicine, Cancer Institute Hospital

Radiologic, macroscopic and histologic studies

were made on 105 lesions of gastric cancer, with

their center localized in the distance of 2 cm from

the esophago-cardia junction (ECJ), resected and

pathologically examined in Cancer Institute Hos-

pital during the period of 15 years from 1965 to

1979.

This figure accounted for 13.2% of 797 lesions

located in C area (according to C.M.A. classifica-

tion) and 3.4% of 3134 lesions detected in the whole

stomach. Of 105 lesions, 74 belonged to male and 31

to female patients, showing the occurrence in male

outnumbered that in female by 2.4 times. Averaged

age of the patients was 57.9 years old (male-58.4

years old; female-56.7 years old).

Macroscopically, 94 lesions were advanced com-

prising 89.5% of 105 lesions with the fructuation

showing 37 elevated lesions ( 3 9 . 3 % ) o f Borrmann

types 1 and 2, and 57 depressed lesions (60.7%).

The remaining 11 lesions were early cancer compris-

ing 10.4% with the fructuation showing 5 elevated

lesions (45.5%) and 6 depressed lesions (54.5%).

Histologic study revealed 64 out of 94 lesions of ad-

vanced cancer were differentiated (68.1%) and 30

were undifferentiated (31.9 %). Of 11 lesions of early

cancer, 8 were differentiated (72.7%) and 3 were

undifferentiated (27.3 %).

Each of 1 lesion of type I and 2 lesions of type IIa

early cancer, located within 1 cm distance from ECJ,

was radiologically revealed as a small circular or

semi-circular filling defect as the column of contrast

medium passed through the esophagus. These

findings were absent in 6 lesions located in the dis-

tance between 1.1 cm and 2.0 cm from ECJ. Of these

6 lesions, 1 of type IIa and 2 of type IIc were located

on the lesser curvature aspect, and 3 lesions of type

IIc were on the posterior wall aspect. All of them

were delineated by double contrast method with the

patients in the supine, left anterior oblique position

to the almost right lateral decubitus.

We reached the conclusion that in order to detect

early cancer radiologically, (i) we should make ob-

servation first at various positions on the horizontal

level. Then a close observation in the course of posi-

tional change from the horizontal to the semi-

August 1981 Proceedings of 22nd dutumn Meeting 417

upright is most important in both cases of depressed and elevated lesion; (ii) we should closely observe the flow of contrast medium when it passes through the lower esophagus into the cardia, making the posi-

tional change from the supine horizontal to the left anterior oblique or the reverse, if the case is of ele-

vated lesion adjacent to ECJ.

X-ray diagnosis leading to early detection of gastric cancer of the cardiac region

Tozo HOSOI and Tsutomu HAMADA* Tokyo Metropolitan cancer Detection Center

*Department of Internal Medicine, Juntendo University School of Medicine

Sixteen lesions of early gastric cancer of the car- diac region detected by Tokyo Metropolitan Cancer Detection Center and the Department of Internal Medicine, Juntendo University over the past ten years were investigated. These lesions represent 2.4% of total early gastric cancer lesions (675 cases),

and include both elevated (5 cases) and depressed (11 cases) type lesions.

Diagnostic results based on routine and thorough X-ray examination of these 16 cases were carefully analyzed; the findings were then used as a tool for considering the most effective means of radiograph-

ing and interpreting radiographs to detect early gas- tric cancer of the cardiac region.

Results: A. Photographing Elevated type lesions about 5 mm in diameter are

best revealed by photographing when a weak bar ium solution (60-80 w/v%) passes through the cardiac region in a half-standing, left anterior ob- lique position.

Depressed type lesions are best revealed in the same position, but the barium-coated cardiac region should be filled with a medium quantity of air.

B. Interpreting A 3-dimensional X-ray image must be mentally

constructed in order to detect depressed-type lesions of early gastric cancer in the cardiac region.

X-ray images of the cardiac portion were clas- sified into 3 types: open, semi-closed, and closed.

Progress toward the effective diagnosis of early

gastric cancer of the cardiac region was made by

interpreting X-ray images on the basis of the above 3 classifications.

X-ray diagnosis of early cancer in the upper portion of the stomach

Yoshinori SUGINO and Kenji KUMAKURA

Department of Diagnostic Radiology, School of Medicine, Keio University

Twenty-six cases of early cancer in the upper por- tion of the stomach ("C-area"), containing 5 cases in the cardiac area which defines the gastric portion within 2 cm from E-C junction, were radiologically evaluated for the early diagnosis. I. X-ray apparatus:

We have reformed the X-ray apparatus from the

various points of view--in 8 items. Such improve- ments have lead to higher resolusion of the X-ray

pictures and minute lesions could be identified even by fluoroscopy. So dynamic observation of bar ium study became possible, and these are useful for the

early diagnosis for the lesions in the upper gastric portion. II. Examination method for the upper portion of

the stomach: A. Routine study. 1. Fluoroscopic observation

and shooting at the time of the contrast media passing through the cardiac area. 2. Double con- trast study in the upright position. 3. Double con- trast study in the LAO to right-side-down position-- Fluoroscopic observation is very important dur ing changing the patient's position. 4. Double contrast

study in the prone position. B. Close examination. 1. Double contrast study

for the cardiac area in the right-side-down posi-

tion with minute adjusting the patient's position for the bar ium passing through the lesions. 2. Double contrast study for the upper portion of the stomach except for the cardiac a rea - - in the supine, LAO,

right-side-down and prone positions and these posi-

tions should be employed according to the location of the lesions.

References

1) Kumakura K, et al: The bettering approach to

418 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

the X-ray apparatus of clinical pictures in the

early gastric cancer diagnosis. Stomach & Intes-

tine 14: 13, 1979

2) Kumakura K, Takagi T: Early diagnosis of

stomach on upper region. Jpn J Cancer Clin

Suppl, 180, 1965

3) Sugino Y, Kumakura K: Diagnostic problems of

cardiac cancer from the standpoint of radiology.

J Clin Surg 34(12): 1799, 1979

The diagnostic technique on the small

gastric carc inoma in the

upper segment

Hiroto N I S H I M A T A and Toshiaki MISONO

The Second Department of Internal Medicine, Faculty of Medicine, Kagoshima

University, Kagoshima

In this study, the upper segment of the stomach

was defined as the area of the cardiac gland mucosa

within 2 .0cm from the esophago-gastric junction

and the fundus.

The investigation on diagnostiic technique was

performed radiologically and endoscopically for the

purpose of making diagnosis of small gastric cancer

Type IIc located in the upper segment of the

stomach. The subjects of this study were 12 cases of

gastric carcinomas Type IIc less than 3 .0cm in

diameter (including 2 cases of microcarcinoma less

than 0 .5cm in diameter). All these cases were re-

sected and examined histologically by wholly step-

wise sectioning.

Conclusion: i) It is effective to take spot films in

the half standing, prone, left anterior oblique pro-

jection or left anterior lateral view, the right ante-

rior oblique projection, the frontal view and the

right anterior oblique projection.

ii) The down management of the fiberscope is

useful for the observation of gastric carcinoma

around the esophago-gastric junction and the

fundus.

Endoscopic diagnosis of early gastric

cancers in the upper por t ion of

the stomach

Masaharu T A T S U T A and Shigeru OKUDA

Department of Gastroenterology, The Center for Adult Diseases, Osaka

With the widespread use of endoscopic gastric

biopsy and cytology under direct vision in the diag-

nosis of gastric cancer, early gastric cancer is recog-

nized with increasing frequency. In the upper por-

tion of the stomach, however, advanced cancers

were more frequently found than those of early

stage. In the present paper, the relation of the upper

fundal gastritis to the gross and histological types of

early gastric cancer located in the upper portion of

the stomach and the endoscopic diagnostic accuracy

of the gastric cancers in the cardiac portion were ex-

amined. Early gastric cancers in the cardiac portion

were defined as early carcinomas located within

2 cm from the esophago-gastric junction.

Results: 1. Early gastric cancers in the cardiac

portion were found in 9 patients. The cancers were

frequent in patients of 60 years old or more, and

were more often grossly elevated.

2. A close correlation between the gross and his-

tological type of early gastric cancer in the cardiac

portion and the presence or absence of the upper

fundal gastritis. In general, when atrophic gastritis

was not found in the upper port ion of the stomach

and, therefore, the cancers were located in the acid-

secreting areas, the cancers were ulcerated and his-

tologically poorly differentiated. On the contrary,

when atrophic gastritis was observed arround the

cardia and, therefore, the cancers were located in

areas of fundal gastritis, the cancers were elevated,

and histologically differentiated and intestinal type.

3. By routine endoscopic examinations a correct

diagnosis was provided in all cases of early gastric

cancers in the cardiac portion. At the first examina-

tion, however, the lesions were missed by the endo-

scopy in 2 cases of these, and biopsy was unsuccessful

in another 2 cases.

4. Early gastric cancers located on the

esophago-gastric junction were missed by the side-

viewing fiberscope, but a correct diagnosis was easily

made by the forward-viewing fiberscope. A correct

diagnosis was achieved in cancers located within

1 cm from esophago-gastric junct ion during the

retroflexive visualization of the cardiac portion by

the side-viewing fiberscope. Downward direction of

August 1981 Proceedings of 22nd Autumn Meeting 419

the side-viewing fiberscope makes easily a correct

diagnosis of early gastric cancers located 1 cm or

more f rom the esophago-gastric junc t ion .

5. Combina t ion of the rout ine endoscopy with

retroflexive visualization of the gastric fundus, and

with dyeing endoscopy (e.g. Congo red-methylene

blue test developed in our clinic) raised the diag-

nostic ra te of early gastric cancers located in the car-

diac or upper por t ion of the s tomach.

Endoscopic diagnosis of early cancer on uppe r t h i r d of the stomach

Misao YOSHIDA and Mitsuo ENDO

Institute of Gastroenterology, Tokyo Womens Medical College

I) Since 1965 to 1978, 862 lesions of early gastric

cancer were resected in the Inst i tute of gastroen-

terology, Tokyo Womens Medical College.

Only 7 .8% of them (67 lesions) had its center on

upper th i rd of the stomach. Macroscopic classifica-

t ion of all early gastric cancers was as follows: IIc

and IIc combined by other type 58.4%, IIa and IIa

combined by other type 21 .5%, III and III com-

b ined by other type 6%, and I Ib 5 .2%. Classifica-

t ion and frequency of early cancers on upper th i rd

of the s tomach was almost same with other port ion

of the s tomach.

II) Oral marg ine of uppe r port ion of the

s tomach is so called fundic area, which is defined as

area l imited within 2cm from esophagogastric

mucosal junct ion. In this area 95 % of gastric cancer

was advanced type, and 91% of them were of Borr.

II or Borr. III type. On the o ther hand, early cancer

on fundic area were only five cases, and most of

them showed elevated type (I-type is one case and

IIa- type is three cases).

III) Endoscopic observation for early diagnosis

of gastric cancer on upper th i rd por t ion of the

s tomach should include fundic area as well as close

observat ion of the s tomach.

Forward-view type panendoscope fits for those

purpose.

Panel Discuss ion:

M u l t i p l e I m a g i n g D i a g n o s i s i n t h e B i l i a r y T r a c t :

C o - M o d e r a t o r s : Dr . K i y o h a r u N I S H I O K A a n d Dr . Yasuak i T A K E H A R A

The diagnostic accuracy and l i m i t a t i o n of

excretory c h o l a n g i o g r a p h y in the diagnosis of cho le l i th ias i s

Yasuhiro NAKASHIMA and Yoshifumi KODAMA

The Second Department of Surgery, Kagoshima University Faculty of Medicine

A grea t stride in the diagnosis of gallstone diseases

has been established following the development of

h igh-qual i ty grey scale u l t rasound equ ipment and

o ther procedures in recent years.

Nevertheless, the excretory cholangiography is

still first-choice examina t ion demons t ra t ing biliary

tree as a whole. In the present series, 236 preopera-

tive intravenous cholangiograms combined with

oral cholecystograms were analysed retrospectively

in order to elucidate their diagnostic accuracy and

l imi ta t ion in opacifying bil iary tract. Positive diag-

nosis were obta ined in 67.4 per cent of cholelithiasis

(159 out of 236 cases). It was 76.0 per cent in chole-

cystolithiasis, (127 out of 167 cases), 52.7 per cent in

choledocholithiasis (29 out of 55 cases) and 21.4 per

cent in the hepatoli thiasis (3 out of 14 cases). Ac-

cura te diagnosis of cholelithiasis has been estab-

lished in 76.0 per cent of f cholesterol stones (111 of

145 cases) and 52.7 per cent of p igment stones (48 of

91 cases).

Upon location of stones, visualization rate of

cholesterol stones in the ga l lb ladder were 80.0 per

cent, 99 out of 124 cases; 57.1 per cent in common

bile duct, 12 out of 21 cases, while tha t of p igment

stones were 65.0 per cent, 23 of 43 cases in gallblad-

der; 55.9 per cent; 19 of 34 cases in c o m m o n bile

duct ; 21.4 per cent, 3 of 14 cases in in t rahepat ic cal-

culi.

420 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

Thus, intravenous cholangiography demonstrated

good visualization rate and since newly developed

contrast media such as Chlegraffin and Bliliscopin

had less hazard than Biligrafin, excretory cholangio-

graphy should be done prior to biliary tract surgery

to get precise information concerning intra- and

extrahepatic biliary tract as a whole.

Reference

1) Kune GA, Sali A: The practice of biliary sur-

gery. Second Edition, London, Blackwell

Scientific Publications, 1980, P 62-71

Significance and limit of drip infusion cholangiography in the diagnosis

of cholelithiasis

Hiroshi T A N I M U R A and Yorinori HIKASA

The Second Department of Surgery, Kyoto University School of Medicine

It is necessary to perform an appropriate surgery

of cholelithiasis for the prevention of residual or

recurrent stones, and most important to recognize

the location and exact numbers of gallstones and the

dilatation of the bile duct preoperatively. On in-

cluding the patients with severe pain, fever and /o r

jaundice, the diagnostic method has to be noninva-

sive, simple and short in time as possible. Signifi-

cance of drip infusion cholangiography (DIC) was

discussed retrospectively in 3313 cases operated at

our clinics during 5 years. The following results were

obtained.

1) DIC was performed in 75.3% of cholecysto-

lithiasis, and 80.7% of choledocholithiasis. ERC in

32.7% and PTC in 14.1% of the later cases were

added. Ultrasonography (US) was done similarly

frequently between two groups.

2) Final diagnosis was established in 69.6% to

70.2 % of gallbladder stones and 48.4 % to 49.2 % of

bile duct stones by DIC, independently the previous

oral cholecystography. Although the other cases re-

quired US, ERC and /o r PTC, each adequate opera-

tion was performed by DIC alone in 2135 (64.5%) of

total cases.

3) Clinical trials with iodoxamate and iotroxate

were presented as new contrast media which give

more rapid excretion into bile and clearer chol-

angiograms with less severe side effects than Bili-

grafin.

Reference

1) Tanimura H, et al: Drip infusion cholecysto-

cholangiography y with iodoxamate III. Espe-

cially compared with iodipamide. Arch Jpn Chit

46: 313-325, 1977

Integrated imaging on biliary tract diseases. 3. Ultrasonography on

bile duct disorders

Harutaka ITAYA and Morimichi FUKUDA

The Fourth Department Medicine, Sapporo Medical College

Diagnostic use of grey scale ultrasound has been

well establishedded as one of the diagnostic

modalities of biliary tract diseases especially since

the introduction of high-resolution real-time scan-

ner and high-resolution contact scanner. The

method is especially suited for the investigations of

gallstone and malignant tumors of the biliary tract,

both of which often required the use of more inva-

sire techniques such as ERCP and PTC. Diagnostic

rates of cholecystocholelithiasis and obstructive

jaundice ww were 98% and 95%, respectively. It is

often difficult, however, to visualize the lower parts

of the bile duct due to the intervening gas echoes

present in front of the pancreatic head. Among

several measures tested, careful manipulat ion of

high-resolution real-time scanner at the various

positioning, coronal scan by Octoson and the use of

the echoendoscope were effective to visualize the

common duct area. Integrated imaging of the bile

duct system can be constructed based upon facilities

and man power of the respective institutions, the use

of ultrasonography in the early parts of the decision

tree is stressed.

Evaluation of computed tomography in the diagnoses of biliary tract diseases

Kiyoshi INOUE and Akio MORI

Department of Gastroenterology, Shizuoka Rosai Hospital

August 1981 Proceedings of 22nd Autumn Meeting 421

Livers from autopsy cases were sliced in one centi-

meter thickness after injection of contrast medium

in the bile ducts to compare with the figures from

computed tomography (CT) scans. In this slice

study, each position of the triad (portal vein, hepatic

artery and biliary tract) was examined and clarified

by the continuous follows of each slice. With this

basic anatomical knowledge, CT scans were per-

formed in 895 patients with C T / T 7800 and C T / T

8800. CT is sensitive to the dilatation of either intra-

hepatic or extrahepatic bile duct and is of value to

identify the location of the obstruction, though diffi-

culty is present in showing the quality of the lesions

other than the high density stones. Even the low den-

sity stones, however; can be demonstrated by the

careful display having knowledge of normal location

of biliary tract in CT.

Additionally, we arranged the Hydrochol |

Padr in | | enhancement method which is

effective on demonstration of the gallbladder and

the biliary tract. Gallbladders in 132 of 162 (81%)

cases and common ducts in 100 (62%) were more

evident after the enhancement compared with the

Conray | enhancement controls. Even thickness of

the gallbladder wall was clearly visualized in some

cases by this new method.

Significance of ul t rasonic examina t ion

and ul t rasonical ly guided punc tu re

in diagnosing b i l ia ry

tract diseases

Yasutsugn BANDAI and Masatoshi MAKUUCHI*

The Second Department of Surgery, University of Tokyo

*Department of Surgery, National Cancer Center

Studies were made in 407 cases of biliary tract dis-

eases for diagnostic accuracy of ultrasound. The de-

cision tree for diagnosis of biliary tract diseases was

presented combining ultrasonically guided percuta-

neous transhepatic cholangiography (UGPTC) and

biliary drainage (UGPTBD). Detectability of gall-

stones was 93%. Even in cases with negative chole-

cystogram that was 87 %. Pictures of polypoid lesion

and carcinoma of the gallbladder were obtained

more than 90 %. Detectability of choledocholithiasis

was very low (30%). Accuracy of differential diag-

nosis of jaundice was 97%; however, the lesion

which caused obstruction could be depicted only in

47%. Therefore, direct opacification of the biliary

tract was inevitable. UGPTBD which we devised

need not PTC and do not elevate intrabiliary pres

sure, so that safer drainage can be accomplished.

On that ground, once the' diagnosis of obstructive

jaundice is made, UGPTBD should be done as soon

as possible. Then the lesion is scrutinized by opacifi-

cation through the drainage tube. On the other

hand PTC was also performed under ultrasonic

guidance which made it possible to puncture bile

ducts selectively and application of PTC became to

be confined to hepatolithiasis in which the distribu-

tion of stones is different from patient to patient. On

the basis of these data, the decision tree was pro-

posed as follows. The lesions of gallbladder are diag-

nosed only by ultrasound except the cases in which

the gallbladder are not demonstrated or in which

malignant disease are highly suspected. In such

cases other diagnostic procedures are necessary.

About half of the cases with lesions of the bile ducts

can be diagnosed by ultrasound. Next step is intra

venous cholangiography in non-jaundiced patients

and is UGPTBD in jaundiced patients. Endoscopic

retrograde cholangiography and angiography

should be performed for more precise assessment for

surgery. In cases with hepatolithiasis, abdominal

plain film or CT scan may be necessary for differ

entiation from pneumobilia. After that UGPTC is

best modality for precise assessment.

Imaging diagnosis of biliary tract with

special focusing on E R C P

Kozo TAMAI and Kazuya UENO

The Second Department of lnternal Medicine, Shinshu University School of Medicine

This paper presented the studies on ERCP in

terms of its manipulation, diagnostic evaluation and

safety on the basis of 2053 cases performed at the

2nd Department of Internal Medicine, Shinshu Uni-

versity School of Medicine.

"Straight scope position" method was generally

422 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

applied on the insertion of fiberscope. This method

was found to decrease the patients' complaint as well

as to increase the successive rate of cannulation into

bile duct and also to spare the time of procedure.

Among the total cases undergone ERCP, cholangio-

graphy was obtained in 77.3%. However, when

aimed to get chiefly cholangiography, the successive

rate was much high as 94.3%.

On the other hand, an ultrasonic (US) diagnosis

method was superior to ERCP for cases whose gall-

bladder was negative on ERCP. But when taken into

consideration that the patients with gallbladder can-

cer had not infrequently a malformat ion of pancre-

aticobiliary ductal system, the sufficient examina-

tion by ERCP seemed to be necessary prior to sur-

gical intervention. Futhermore, as is well known, the

disease of the biliary tract are frequently accom-

panyed with pancreatic disease and vice versa, the

ERCP which can detect both biliary and pancreatic

duct at same time with biliary-pancreatic disease.

With respects to the safety of ERCP, a severe com-

plication of the bile duct system was noted in only

two cases (0.097%).

Diagnostic accuracy of obstructive jaundice using various diagnostic

modalities

Tohru ISHIKAWA and Hiroshi ASHIDA

Department of Radiology, St. Marianna University School of Medicine

Purpose: The purpose of this paper is to compare.

diagnostic accuracy of obstructive jaundice using

various diagnostic modalities.

Method and Material: Sixty three cases of ob-

structive jaundice was analyzed, using liver scan, US

and CT.

Results: 1. Sensitivity for dilatation of biliary tree

of liver scan, US and CT were 77.8%, 91.8% and

100 % respectively.

2. Sensitivity for site of obstruction of US and

CT were 89.8% and 100%.

3. Sensitivity for pathology of obstruction was

better in CT than US.

4. Various cases of pathology were demon-

strated.

Conclusion: CT gives more information than US

in obstructive jaundice.

The diagnosis of extent of bile duct carcinoma

Seikoh SHIMAGUCHI and Joe ARIYAMA

Department of Gastroenterology, Juntendo University

The extent of 28 proved bile duct carcinoma was

studied by means of double contrast study of the bile

duct, angiography and CT scanning. Findings of

each modality was compared with histology. Intra-

ductal spread of bile duct carcinoma was studied

with double contrast study of the bile duct. Barium

sulfate and carbon dioxide were injected through

percutaneous drainage catheter into the bile ducts

and double contrast study was performed. Extra-

ductal extension of carcinoma was studied magnifi-

cation superselective angiography of the gastroduo-

denal, proper hepatic and /o r cystic artery. CT scan-

ning was carried out using EMI 5005. Double con-

trast study of the bile ducts was useful to define ex-

tent of intraductal extension of carcinoma. Correct

diagnosis was established in 26 (93%) of 28 patients.

Demonstration of normal mucosal pattern of the

bile ducts with double contrast study is indispens-

able to diagnose intramucosal or intraductal

metastasis of carcinoma. Extraductal extension of

carcinoma was accurately assessed by angiography

in 26 (93%) of 28 patients. It was possible to diag-

nose extraductal extension in 6 (66%) out of 9 pa-

tients with CT scanning. CT was suited to demon-

stration of large unresectable bile duct carcinoma.

A current state of various methods of visualizing the gallbladder and bile

ducts and decision flow charts for diagnostic evaluation

of diseases of the biliary tracts

Masao YOSHII and Kanji TORIZUKA

Department of Radiology ~ Nuclear Medicine Kyoto University Hospital

We investigated the current state of various

August 1981 Proceedings of 22nd Autumn Meeting 423

methods for visualizing the gallbladder and bile

ducts based on the recent data of them. Oral chole-

cystography detects only a small part of cholecysto-

lithiasis and let most cases remain suspicious or non-

visualization of gallbladder. DIC (Drip Infusion

Cholangiography) is superior to oral cholecysto-

graphy and useful in evaluating the lesions of chole-

dochus. Sonographic imaging (U.S.) of the biliary

tract is most useful method for detection of stones in

the gallbladder and bile ducts. U.S. also evaluate

tumors of biliary tracts and lesions of intrahepatic

bile ducts, but it seems somewhat difficult to detect

stones in the distal common bile duct. ERCP pro-

vides best information about lesions of common bile

and hepatic duct. 99mTc-pyridoxylidene isoleucine

(PI) Scintigraphy is widely used for post operative

patients with cholecystectomy with choledochoduo-

donostomia to visualize the flow or dynamics of bili-

ary excretion and for patients with slight jaundice

and liver dysfunction to define lesions. Computed

Tomography (CT) evaluates most lesions of gall-

bladder, especially gallbladder cancer, but do not

detect stones in gallbladder and common bile duct

in one-third of the cases. Finally we tried to make

decision flow charts for diagnostic evaluation of dis-

eases of biliary tracts setting U.S. as a first choice.

Diagnosis of biliary diseases by real- time ultrasonography and direct

cholecystocholangiography

Yukihiro TSUCHIYA and Masao O H T O

Department of Medicine, Chiba University School of Medicine

The great advances in recent years in the diagno-

sis of the biliary diseases include direct cholecysto-

cholangiography (CC) as PTC and ERC, and real-

t ime Ultrasonography (US), We studied the correla-

tion between both modalities as follows:

I. Ultrasonography

US alone diagnosed extrahepatic obstruction in

101/102 patients. In one patient ERC was essential

for correct diagnosis. Cause of obstruction was as-

sessed in 69/102 (26/35-upper obstruction, 43/67-

lower obstruction). These results imply that the

combination of US and direct CC will secure more

correct diagnosis than either method alone.

II. US guided PTC and aspiration biopsy of the

gallbladder

Needle guided by real-time US system permitted

aimed puncture of ducts and vessels smaller than

10mm in diameterl). US guided PTC was per-

formed in 108 patients, and was most applicable to

detailed diagnosis for localized lesion of the intra-

hepatic bile ducts as hepatolithiasis for localized

lesion of the intrahepatic bile ducts as hepatolithia-

sis and for lesion of nonfunctioning gallbladder. In

retrospective study of 17 patients with carcinoma of

the gallbladder, aspiration biopsy proved malignant

cells in 15. US guided aspiration biopsy served the

final diagnosis.

III. US guided percutaneous bile drainage (US-

PBD)

US-PBD was performed in 111 patients with ob-

structive jaundice and /o r suppurative cholangitis.

This technique offers a great advantage over the

previous X-ray guided one as follows: US permitted

direct catheterization of the biliary tract without

opacification and avoidance of puncture of larger

blood vessels of the liver. US guided puncture made

the PBD safer and more reliable.

1)

Reference

Ohto M, et al: Ultrasonically guided percuta-

neous contrast injection and aspiration biopsy

using a real-time puncture transducer. Radio-

logy 136: 171-176, 1980

The study on the diagnosis of biliary tract carcinoma, special reference

of direct cholecystography ultrasonically guided

puncture

Munemasa RYU and Hiroshi SATO

The Second Department of Surgery, Chiba University School of Medicine

Since the wide application of PTC and ERCP,

many cases of biliary tract carcinoma have been ex-

perienced. But almost cases have been diagnosed at

late stage of biliary tract carcinoma. From 1973 to

1980, 95 cases of biliary tract carcinoma have been

424 Proceedings of 22nd Autumn Meeting Vol. 16, No. 4

experienced (35 cases of gallbladder carcinoma and 60 cases of bile duct carcinoma). In diagnosis of gallbladder carcinoma, only 4 cases were easily diagnosed by PTC or ERCP with tumor shadow in gallbladder. The other 31 cases with negative chole- cystogram were difficult to obtain correct diagnosis by PTC or ERCP. In diagnosis of bile duct carcino- ma, 16 cases of middle and distal carcinoma were easily diagnosed with positive cholecystogram, but in upper and wide spread carcinoma, 25 of cases

with negative cholecystogram by combined use of

PTC and ERCP were difficult to obtain correct diagnosis. For the purpose of obtaining correct diag-

nosis and eary diagnosis of biliary tract carcinoma,

we aggressively carry out. Ultrasonic examination and direct cholecystography by ultrasonically guided puncture. This procedure can be performed safely through the liver because of seeing the needle echo during puncture. We have employed direct cholecystography by ultrasonically guided puncture in 72 cases. Since this procedure has been carried out, we get high resetted rate of 79%, 15 of 19 cases, in gallbladder carcinoma. This procedure is effec- tive for the accurate differential diagnosis between gallbladder carcinoma and bile duct carcinoma, and also effective for the diagnosis of gallbladder carcinoma in early stage. This procedure should be

aggressively carried out in negative cholecystogram.

Image diagnosis of hiliary system. Comparative values of severaLimaging

methods and "decision tree" with ultrasonography

at the base

Yasuo NAITO and Eizo KIMOTO The Second Department of lnternal Medicine,

Nagoya University School of Medicine

For the purpose of discussing the value of ultra- sonography in the diagnosis of biliary diseases, the diagnostic efficacy of ultrasonography was studied in comparison with drip infusion cholangiography (DIC), percutaneous transhepatic cholangiography

(PTC), endoscopic retrograde cholangiopancreato- graphy (ERCP), hypotonic duodenography (HDG), hepatic angiography and computed tomography (CT).

A total of 1155 patients with biliary disease were

examined with at least one of these procedures. Ultrasonography was performed in 547 of the pa- tients.

Ultrasonography provided with useful informa- tion regarding the gallbladder, intrahepatic bile

duct and the upper part of the extrahepatic bile duct, and diagnostic accuracy for lesions in these portions of the biliary system was not less than 80 %. Although ultrasonography has a definite limitation in detecting the lesions per se existing in the lower portion of the extrahepatic bile duct, informations obtained by ultrasonography, whether the bile duct was dilated or not, for example, provide with guides to the selection of diagnostic procedures to follow.

Furthermore, percutaneous puncture of biliary

system can be performed more safely and selectively under ultrasonic guidance than under fluoroscopic control. More detailed and definitive findings of bili-

ary tree can be obtained by PTC and/or ERCP if only the bile duct is successfully opacified.

Angiography proved to be efficatious in eluci- dating the extent of carcinomatous lesion in the liver

and the gallbladder, but of limited value for lesions involving the extrahepatic bile duct.

Computed tomography well delineated calculi and tumors within the liver.

Combined use of HDG, ERCP including endo- scopic biopsy and PTC made it possible to diagnose the lesion of the papilla accurately.

Ultrasonography is not only non-invasive and easy to perform but also gives useful informations, some of which would never be allowed by any other con- ventional diagnostic measures.

It might well be concluded that ultrasonography should be employed as the initial diagnostic test in diagnosing biliary disease, and that further investi- gative procedures should be planned according to

the informations obtained by ultrasonography.