General Lectures-(II

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Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(H) Tab. 3.

I n c i d e n c e o f Au-Antigen in L i v e r D i s e a s e

Alcoholic Liver Injury Fulminant Hepatitis Subacute Hepatitis Acute Viral Hepatitis Persistent Hepatitis Chronic Hepatitis active Type Inactive Type Biopsy not performed Hepatic Cirrhosis Hepatoma Other Hepatobiliary Dis. Non Hepatic Disease

Examined Case No. 28 11 8 94 18 61 {30 15 16 36 12 150 43

present in 28 cases (62.2%) and slight polymorphonuclear cell infiltration was found in 34 cases (75.6%), except a few cases where moderate to severe infiltration were detected. Type of fibrosis was dominantly pericelluar, characterizing alcoholic liver injury. Cirrhosis was present in 7 cases. Hemosiderosis, cholestasis and bile duct proliferation were seen in 28 cases (62.2%), 18 cases (40.0%) and 33 cases (73.3%), respectively. Au-Ag was positive in only two cases (7.1%). In one case of heavy drinker with Au-Ag, marked mononuclear cell infilt-

Au-Antigen Positive 2 5 2 30 4 20 {1i 11 7 6 1

% 7.1 45.4 25.0 31.9 22.2 32.8 [46.7 j 13.3 [25.0 30.6 58.3 4.0 2.3

ration and bile duct proliferation with periportal and central zonal necrosis were observed. In the other case with positive. Au-Ag, besides periportal zonal necrosis and inflammatory changes marked fatty metamorphosis was found. Periportal and/or central zonal necrosis detected in these two specimens from Au positive patients were never found in other cases. Therefore, in Au-Ag positive cases of heavy drinker with zonal necrosis, the hepatic changes are probably due to hepatitis virus and alcohol is considered as an aggravating factor.

- - G E N E R A L L E C T U R E S - - (II) (113) COMPARATIVE ANALYSIS BETWEEN ENDOSCOPIC AND R A D I O L O G I C FINDINGS OF THE GASTRIC " H E M O R R H A G I C EROSION" Y. Karasawa, H. Onuma and H. Suzuki

Karasawa Hospital, Asahikawa Hokkaido, Japan T. Okazaki

Okazaki Hospital, Nayoro, Hokkaido, Japan A. Yasui and T. Murakami

Department of Surgery, Juntendo University School of Medicine, Tokyo ,Japan

We hav often presented endoscopic findings of the gastric "Hemorrhagic Erosion" (H.E.) Now, more than 120 cases of H.E. have been experienced endoscopically during the past 7 years. 93 cases of them, which revealed irregular-shaped, wide-spread blackened lesion were analysed comparatively between endoscopic and radiologic findings. 4 cases were illustrated. Case 1: 22-year-old female, complained of severe epigastric pain. Case 2: 35-year-old man, complained of severe epigastric pain. Case 3 : 44-year-old man, complained of

Proceedingsof the 58th Annual Meeting, 1972-- Tokyo--( H) severe epigastric pain and hematemesis. Case 4: 30-year-old man, complained of severe epigastric pain. Endoscopically, in each of illustrated cases was observed an irreguler-shaped wide-spread blackened lesion, which spread from the angulus over the pyloric antrum. These findings substantiates the endoscopic diagnosis of H.E. X-ray examination revealed as follows: (1) Barium-filled radiograph in upright position showed that the pyloric antrum looked sylinder-like and got stiff in spite of injection of Buscopan. (2) Double contrast radiograph in supine position showed lacking of extension of the pyloric a n t r u m in spite of fullness of the stomach with air, indistinct shade of gastric folds where barium adheres to the mucosal surface in a irregular fashion. These radiologic findings can suggest the diagnosis of the gastric H.E. Moreover, their chief complaint and existence of tenderness in the epigastrium are of great value for the clinical diagnosis of H.E. 6 patients with H.E. ,.ere performed gastrectomy, becouse of, frequent severe epigastric pain, ulceration after H.E., or their desire. Case 4 is such a one. O n laparotomy the pyloric antrum of the stomach showed sausagelike mass by palpation. Macroscopically, a section on the greater curvature of the resected stomach was edematous. Histology of the resected specimen showed a marked edema in submucosal and subserosal layer. In conclusion, sylinder-like and stiff condition of the antrum in spite of Buscopan injection can be established as radiologic feature of the gastric H.E.

(114) A C L I N I C O P A T H O L O G I C A L STUDY ON SPECIFIC TYPE OF EROSIVE GASTRITIS K. Furuya

Dept. Surg. Isehara Kyohdoh Hospital Kanagawa Pref.

161

The lesion of erosive gastritis (E.G.) is recognized in 43 of 238 resected specimens which were operated upon under the diagnosis of benign peptic ulcer. T h e incidence of G.E. is 15/ 152 in gastric ulcer, 18/65 in duodenal ulcer and 10/21 in combined gastroduodenal ulcers. E.G. could be classified into protruded and depressed types. In this protruded type, three cases are grossly uneasy to differentiate from the early gastric carcinoma. All of them are revealed to have hyperchlorhydria with the gastric juice analysis. On the gastroendoscopic study, the small sized protrusion with the central shallow erosion is observed in the prepyloric lesser curvature, and it extremely simulated I I a + I I c type of early gastric carcinoma. The gross pathology of the resected stomachs shows that they have all duodenal ulcer and solitary doughnut shaped protrusions in the prepyloric region. These protrusions are larger in size than the usual verrucosa lesions which are multiple and observed at the E.G. frequently. Fixed specimens show these protrusions to resemble to the small sized ttorrmann 2 type of gastric carcinoma. Histological study reveals that the protrusion consists of hypertrophy of pyloric gland with central erosion, where the fibrin is recognized. Neither intestinal metaplasis of the superficial epithelium nor hypertrophic change of the mucosal lymph follicle is found. O f course there are no evidence of malignancy in the pathological study. To differentiate these two lesions, specific type of erosive gastritis and gastric carcinoma, it is necessary to perform endoscopic biopsy. (115) E R O S I O N T O U L C E R : A CLINICOPATHOLOGICAL STUDY O N M U L T I P L E U L C E R S IN GASTRIC ANTRUM K. Furuya

Dept. Surg. Isehara Kyohdoh Hospital Kanagawa P @ M. Ohtsuki

M. Ohtsuki

Ohtsuki Hospital, Tokyo.

Ohtsuki Hospital, Tokyo

While the usual chronic gastric ulcer is al-

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most solitary and located around the gastric angle, the multiple ulcers can be recognized occasionally in the region of pyloric gland scatteringly in the antrum. We have experienced eight cases of these multiple ulcers, which are associated with multiple erosions (UL-I). Some clinicopathological study is performed on these cases, with reference to the ulceration developing from shallow erosion. The resected stomachs of these cases show to have duodenal ulcer. In the antrum small ulcers, three to eight in number, are found predominantly along the lesser curvature. Histologic evaluation reveals that these multiple ulcers are shallow, limiting to submucosal layer (UL-2) and to proper muscular layer (UL-3), and these erosions are deep enough to reach Tunica Muscularis Mucosae (m.m.), which have occasionally inflammatory cellular infiltration and remarkable hemorrhage. The destruction of m.m. is easily supposed to occur following these inflammatory and hemorrhagic changes and the ulceration seems to develope more deeply to UL-2 and -3. In these cases the deep ulcer demolishing the whole layer of proper muscle (UL-4) is located only around the angle along lesser curvature. These multiple ulcers have extremely lesser fibrosis and scar formation in their ulcer floor comparing with that of usual solitary chronic ulcers. The various ulcers, UL-1 to -3, can be found simultaneously in these stomachs, which are seemed to suggest the deeper ulceration originated from the shallow erosion. But no evidence, that the erosion alters into the usual solitary chronic ulcer with marked fibrosis and scar formation, can be found. It is reasonable to conclude that these multiple ulcers are different from the usual solitary chronic gastric ulcer in their origin. (116) S T U D Y O N G A S T R I C SECRETION OF GASTRITIS WITH VARIOLIFORM EROSION H. Sata, T. Kondo, H. Takada, K. Kawaguchi S. Sai, S. Takeda,

and M. Kitagawa

Medical Association For Early Gastric Cancer Detection We have already reported as follows; on the standpoint of endoscopic and bioptic followup studies of varioliform erosions of the stomach, mainly characterized by swollen, raised margins with central depression, they can be classified into two varieties: the transient type (gastritis erosiva) and persistent type (gastritis verrucosa). Now, we studied the difference of the gastric secretory function between those two types by the standard histalog test (Histalog 1 mg/kg or 50 rag). I) Compared with transient types and persistent types appeared in the same region of the stomach, the former shows higher average than the latter in basal secretion (BSVR, 13AO) and stimulated secretion (SVR, AO). II) Persistent types (gastritis verrucosa)-@ Persistent types localized in pyloric region show higher average than those spreading to fundic region in both basal secretion and stimulated one. @ Persistent types with central depression show higher level than those without central depression in basal secretion and stimulated one. Then we can say as follows; persistent types with central depression is in active stage and those with none is in inactive stage. III) Transient types (gastritis erosiva)-In the same cases, stimulated secretion at the appearing phase of gastritis erosiva in nearly the same as at the disappearing phase. O n the other hand, basal secretion (BSVR, BAO) at the appearing phase shows remarkably high level but at the disappearing phase extremely lOW. So we can guess that transient types are acute phase of gastritis with varioliform erosions from the gastric secretory study. This fact was confirmed by histological study of gastric mucosa obtained under direct visual biopsy.

Proceedings of the 58th Annual Meeting, 1972 Tokyo--(H) (117) C L I N I C A L S T U D Y O N T H E GASTRIC ANISAKIASIS WITH ACUTE GASTRIC SYMPTOMS T. Morooka, T. Shiraishi, M. Namiki, H. Kawauchi, and K. Nakagawa

The Third Department of Medicine, Hokkaido University School of Medicine, Sapporo Examination by means of the gastrofiberscope of the patients, who came to the clinic due to the so-called food poisoning symptoms such as gastric pain, nausea and vomiting 4 to 6 hours after ingestion of foods with larvae of anisakis, have often revealed the infiltration of the living larvae i--to the gastric wall. Further, we have been able to find the linear figure of the larva by the X-ray double contrast picture. We have experienced 46 cases as such. The present report described their clinical findings and discussed the mechanisms responsible for them. (118) O N T H E 2 CASES O F T H E I N T E R E S T I N G A.T.P. (ATYPICAL E P I T H E L I U M ) L E S I O N OF THE STOMACH

163

an erosion and repair and reconstruction of the tissue occured repeatedly, and then got high grade atypism gradually. 4) It is the most interesting point to imagine what a finding like this case will get to develop the ability to the carcinoma without intestinal metaplasia. C a s e 2: A.T.P. s h o w e d IIc t y p e e a r l y gastric cancer figure on the resected stomach: 52y. Male. This case showed a lesion on the pre-pyloric portion as convergent folds and eroded tips on each club-head swollen of them by X-ray examination (suspicion of IIc type early gastric cancer). The endoscopic examination could not reveal it on account of the interruption of the swollen folds. O n the resected stomach, a lesion was revealed with eroded tip ot" the swollen gathered folds, and it is able to trace the complete circumference of the edge of the depressed lesion. So it is able to say IIc type early gastric cancer, from their view point of the macroscopic findings strictly. But the histological finding was A.T.P. Group I I I I V consisted of U I - I I ulcer. Recently as we have experienced of case report several cases like this, so it is a reason what to present this case.

H. K u r a m a t a et al.

KANAGA WA SEIJIN-B I10 Center, Department of Radiology It is very interesting to know the relationship between A.T.P. and carcinoma. Hereby we present very interesting cases on this point. C a s e 1 : A.T.P. accompanying with gastritis verrucosa. 44y. Female. This case means as follows: 1) There were m a n y elevations (gastritis verrucosa) scattered on the antrum and the pre-pyloric portion. A clinical diagnosis was gastritis verrucosa by X-ray and endoscopic examination. 2) Histological findings revealed the same, namely the elevated lesion to be consisted of the proliferation of the pyloric glands and on their tops or the surroundings no intestinal metaplasia was to be seen. 3) On the surface of this gastritis verrucosa,

(119) A N A N A L Y T I C S T U D Y O N THE SYMPTOMS AND CRITERIA OF EARLY DUMPING SYNDROME . Y. Yamaguchi

2rid Department of Surgery, Jikei University School of Medicine The criteria for early d u m p i n g syndrome are widely variable depending on the institute. Twenty different symptoms were noted to be used in the early dumping syndrome criteria adopted at 9 surgical departments of medical school which have submitted the data for this analysis. Now, all these 20 symptoms were used again by each of these 9 departments on their patients (238 in total) and statistically following symptoms were found to be manifestive of early dumping syndrome, namely; as

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general symptoms cold sweat, palpitation, sleepiness, feeling of oppression in the chest; as abdominal symptoms abdominal pain, diarrhea, and nausea. It was furthermore noted that some cases of innegligible percent had only one but very representative general symptom, therefore "one or more" general symptom(s) should be in the criteria for early dumping syndrome.

(120) O B S E R V A T I O N A T P O S T OPERATIVE PATIENTS OF GASTRIC CANCER T. Kabakino, T. Inokuchi, J. Wakisaka Y. Yamauchi, T. Debuchi W. Ogo C. Yamasaki, M. Sigemori K. Hashimoto, and T. Shirozu

1st Department of Surgery, Kurume University School of Medicine In the operative gastric cancer, 152 patients of gastrectomy or total gastrectomy was follow up from postoperated 3 months 3 years. Reflux oesophagitis was recognized 33.3% of ~ type anastomosis and 2.3% of Rouz Y type anastomosis. 12.9% of resected gastric cancer had diarrhea. They were due to malabsorption of fat and Vagotomy, but they amount to 30~o inelusive of the diarrhea after taking milk. Loss of postoperative weight were recognized 54.3% of resected gastric cancer. Anemia of patient of gastrectomy was recognized 20.5%. The increase of serum L D H activity at patient of the gastric cancer was not too eminent. The increase L D H Isoenzyme was not significant at the patients of gastric cancer. It was difficult that we aspect recurrence of the liver by biochemistory of L D H activity and AL-P. Aldolase. Isoenzyme is desirable rather than Activity Transition of postoperative globulin had relations with recurrence of the gastric cancer and Stage classification. Transition o f postoperative globulin had influence liver d i s e a s e . In half number from three to five survivor

globulin was increased. (121) P O S T O P E R A T I V E L O N G TERM CANCER CHEMOT H E R A P Y (PLCC) F O R GASTRIC CANCER N. Kaibara, K. Inokuchi, K. Soejima, T. Hiyama, and M. Wakita

2nd Department of Surgery, Faculty of Medicine, Kyushu University It is well accepted that administering a chemotherapeutic agent in conjunction with radical surgery is an effective measure to decrease the recurrence rate and enhance survival of patients with cancer of the stomach. In our clinic, the intra-operative upper half body infusion of Mitomycin-C ( M M C ) has been attempted, which was performed by clamping the subrenal aorta for about 20 minutes after intravenous administration of the drug from an anteeubital vein. In euratively operated patients with stage carcinoma, 41.6% of the patients subjected to the clamping technique had 5-year survival rate, compared to 31.3% of the unclamped control. O f particular interest is the fact that 2 to 3-year survivals of the clamped group were as much as two times higher than those of the control. This may be indicative of insufficiency of a single intra-operative usage of the drug, and consequent increase of late death. To achieve more increased survival rate, we proposed the necessity of postoperative long-term cancer chemotherapy (PLCC), in which the patients subjected to the intra-operative adjuvant chemotherapy should receive 10 mg of M M C intravenously every three months for two years in the out-patient clinic. P L C C will serve for not only a goal to enhance survival but a purpose to detect and treat the recurrences as early as possible.

Proceedingsof the 58th Annual 2kieeting, 1972--Tokyo--(H) (122) S T U D I E S O N T H E A D M I N I S T R A T I O N OF P O S T O P E R A T I V E A L I M E N T A T I O N IN PATIENTS W I T H D I G E S T I V E DISEASECHANGES OF A M I N O ACID PATTERNS, LDH, HBD IN S E R U M AND P Y R U V A T E IN BLOODT. Ikemoto, H. Hayasaka, S. Fukui, T. Takeda, N. Aoyama, Y. Takada, Y. Saheki, Y. Yoshida, K. Minagawa, T. Okuyama, S. Yamamitsu and Y. Konishi

1st. D~artment of Surgery, Sapporo Medical College. We studied the pre and postoperative changes of serum LDH, HBD and pyruvate in blood in relation to the metabolism of amino acids in patients with gastric cancer. The results indicate that the changes of SLDH, S-HBD and pyruvate after operation are similar to that of amino acids. Therefore, we can approximately infer the changes of amino acid patterns from the level of S-LDH, S-HBD and pyruvate.

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Barium was injected into the mucosal vessels through an artery under the same observation, then it was fixed and sliced the thickness being 200 /1 in order to do super soft X-ray examination. Acrylic ester was injected from both venous and arterial sides to make microvessel plastics. It was cut at the area of ulcers to compare the changes in each ulcer. Results show that, even though they have different degrees of changes, impaired blood flow from the arterioles to the capillaries, stasis of the venules, and the arterio-venous shunts in the submucosa play a part in the development of ulcers.

(124) V A S C U L A R A R C H I T E C T U R E AND P A T H O G E N E S I S OF G A S T R I C A T R O P H Y AND GASTRITIS: A MICROANG I O G R A P H I C STUDY K. Maruyama, K. Yoshino, T. Suzuki, .K Akisato, M. Kitajima, T. Tabata, M. Hashimoto, T. Tanaka, Y. Nakagawa, and Y. Ishii

Dept. Surg. Keio Univ. (123) E X P E R I M E N T A L PEPTIC U L C E R AND CHANGES OF MICROCIRCULATION N. Ishimatsu, S. Murai, A. Nukaga, S. Toyama, Y. Watanabe, N. Mizushima, and M. Abe

The 4th Department of Internal Medicine (Professor Masakazu Abe, M.D.) Tokyo Jikeikai University of Medicine Reserpine ulcer, steroid ulcer, gastrine ulcer, Curling's ulcer were produced in rats and the following experiments were done. Their stomachs were opened under anesthesia. Evans blue was injected into the artery. During the whole time from the beginning of appearance of Evans blue into the gastric mucosal surface to its disappearance from the surface observations were made by use of stereomicroscope.

Pathogenesis of gastric atrophy as well as gastritis are evaluated with our reformed microangiographic approach, in which the radio -paque medium, solution of barium sulfate crystal and/or colloidal solution of silver iodine, is injected into the blood vessels of the human stomachs resected in surgical operation. In superficial gastritis, it is only recognized the marked dilatation of mucosal vessel, which seems to be due to the inflammatory congestion, without remarkable change of the vascular architecture. Atrophic gastritis could be classified into two groups, glandular atrophy without the hyperplastic change of foveolar epithelium and the atrophy with hyperplastic change of that (hyperplastic atrophic gastritis). In the former, the mucosal vessels are shortened and they have abnormal branching like shrubs and collateral ways. In additin, the vascular network along the muscularis mucosae shows some disorder. These changes are

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seemed to be due to the diminution of gastric gland and fibrosis of mucosa and submucosa. In the latter hyperplastic atrophic gastritis, area gastricae protrudes remarkably owing to the hyperplastic change of foveolar epithelium, from the center of which the vessel rises up like a fountain. But the vessel is scant at the depressed portion between these protruded areae. In hypertrophic gastritis, the vascular pattern resembles to that of atrophic hyperplastic gastritis and markedly elongated mucosal vessel can be recognized in the protruded area. This vessel, however, seems to rise up not in the shape of a fountain but in parallel in each other, which is the diffi'ent point from the atrophic hyperplastic gastritis. Pathogenesis of gastric atrophy have been debated since long ago and seems to be very difficult subject to clarify, and it remains yet unknown now. In our microangiographic study, the factor of blood supply seems to play the great role on this with the change of mucosal lymph follicle. It is observed that the mucosal vessel around the enlarged lymph follicle is oppressed aside, the surface mucosa on the top of the follicle shows the circulatory disturbance and it gives way into surface erosion. It could be speculated reasonably that these disorder induce the destruction of gastric gland, which are followed with various kinds of repairing mechanisms, and that various types of atrophic change of gastric mucosa break out. Although it is very difficult to determine whether the lymph follicle appears primarily as the result of immunological reaction and other factors like that, or it develops secondarily due to the surface erosion, we would like to conclude it to be primary change, for the surface erosion, which is not associated with the lymph follicle beneath it, is able to be found easily and almost all the surface mucosa situated on the top of enlarged follicle seems to have erosive change in various degree.

(125) S T U D I E S O N fi-GLUC U R O N I D A S E IN G A S T R I C JUICE M. Inoue

Fukuoka University and Kashii Hospital, Fukuoka 1) fi-glucuronidase activity in gastric juice was estimated using p-nitrophenyl glucuronide as substrate. Because of no definite optimal pH, on each samples, reactions were performed at the p H of 4.71 5.0, 5.2 and 5.4, and the highest value was adopted as the activity. Enzyme assay was m a d e on basal gastric juice as a rule, however, When the p H was below 6.0, 50 ml. of 1% bicarbonate solution was injected intra-gastrically and aspirated 5-10 minutes later. The latter procedure was repeated on three occasions, and samples with a p H above 6.5 were chosen for analysis. Protein contents were measured by the method of Lowry, and enzyme activity was expressed as unit per mg of protein per hour. 2) The patients studied include 17 with gastric cancer, 33 with gastric ulcer, 12 with duodenal ulcer, 25 with dyspepsia and chronic gastritis, and 8 with miscellaneous diseases (polyps, chronic pancreatitis etc.). 3) 16 out of 17 patients with gastric cancer showed the /~- glucuronidase activities above 6.5 units per m g of protein in their gastric juice, on the other hand, 20% of the patients with peptic ulcer, and 30% of the patients with dyspepsia, chronic gastritis and miscellaneous diseases had elevated fl-glucuronidase activities (above 6.5). In total, 24% of 78 non-malignant patients showed false high levels of enzyme activity. 4) p H activity curves offi-glucuronidase in gastric juice could be classified into three types (one with the optimal p H at 4.7, one at 5.05.2, and one at 5.4), however, specific p H activity curve for malignancy was not found. 5) In the patients with benign diseases, relationship between the enzyme activity and acid output after pentagastrin was observed. In 47 patients wth peak acid output above 5.1 m E q per 30 minutes, 10% had elevated/9glucuronidase activities, on the other hand,

Proceedings of the 58th Annual Meeting, 1972-- Tokyo--( H) in 30 patients with P A O below 5.0, even 50% showed high levels of enzyme activities. Perhaps, the presence of atrophic gastritis might play considerable role in the elevation of flglucuronidase activity in gastric juice. 6) Isozymes of ~-glucuronidase in gastric juice were studied by means of D E A E cellulose column chromatography, and eluted at the beginning with 0.005 M acetate buffer p H 5.0. Afterwards elution buffer was continuously mixed with 0.005 M tris phosphate buffer containing 0.13 M sodium chloride. As the results, a high peak firstly, and secondary a small peak of ~-glucuronidase activities were identified. It was concluded that at least two isozymes of b~-glucuronidase are included in human gastric juice.

(126) O N T H E A N A L Y S I S O F LACTATE DEHYDROGENASE BY E L E C T R O F O C U S I N G - CORRELATION BETWEEN SERUM AND TISSUES LDH PI I S O Z Y M E S - - - -

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L D H activities were significantly inactivated only in the p H region below 4.3. To confirm the validity of the fractionation, the purified L D H 1 and L D H 5 from beef cardiac and skeletal muscle were analyzed by E.F. L D H 1 was separated into three fractions and L D H 5 into two fractions. Either of the purified enzyme showed single band at L D H 1 or L D H 5 position before and after the E.F. In the animal experiment with Yoshida sarcoma inoculated rats, serial pI isozyme determinations were carried out by the use of gel electrofocusing. A peculiar L D H subfraction, which showed acidic pI with L D H 5 mobility, emerged after the 7th day of inoculation. This fraction was also found in the zymogram of tumor cell extract. The marked increase in the total L D H activity observed in tumor bearing rats, therefore, is postulated as the result of appearance of tissue enzyme derived from tumor itself. Similar tendencies were noted in the clinical cases examined and representative cases were presented. It is expected that the use of E.F. in L D H analysis might give a more clear understanding of zymogram changes in malignancy.

S. Katayama, Y. Nakano, and M. Fukuda

Department of Medicine, Cancer Research Institute, Sapporo Medical College (Directed by Pr@ Ichiro Urushizaki) The method of electrofocusing (E.F.) has already found numerous applications in the detailed analyses of various enzymes as well as of other proteins. In a previous report we described pI isozyme patterns of lactate dehydrogenase, which was found to be separated into more than ten discrete fractions and its diagnostic applicability in malignant diseases of the digestive system. Present report describes comparative studies on L D H pI isoenzyme of serum and tissues obtained from respective cases. Results Due to the fact that tissue L D H pI isozymes spread widely after the electrolysis, the effect of p H on the enzyme activities was examined.

(127) T H E Q U A N T I T A T I V E ANALYSIS OF NUCLEAR DNA CONTENTS OF GASTRIC CANCER CELLS M. Takaki et al.

Nagasaki University School of Medicine, Under the direction of Dr. Professor Shiro Osajima (M.D.) The nuclear D N A contents of gastric cancer cells gained by biopsy under direct vision have been estimated using the microspectrophotometry method for these five years. It was revealed that the histogram of nuclear D N A contents on gastric cancer showed broad and multiple peaks. In the present study, the nuclear D N A contents of gastric cancer cells were determined in 95 cases, which were later confirmed his-

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tologically by materials taken at surgical operations. Considering the stages, the d e p t h of involvement, the metastasis to regional l y m p h nodes, a n d celullar or structural atypism, comparison of nuclear D N A contents was m a d e a m o n g those groups divided on histological types such as A d e n o c a r c i n o m a tubulare, A d e n o c a r c i n o m a papillare, A d e n o c a r e i n o m a mucocellulare a n d etc. T h e conclusion is this. I n the groups of A d e n o c a r c i n o m a t u b u l a r e a n d A d e n o c a r c i n o m a papillare, a p p e a r a n c e of polyploidy is more c o m m o n in the later stages t h a n in the earlier, a n d also more frequently seen in the cases with metastasis t h a n without metastasis a n d higher grade atypism t h a n lowers.

(128) S T U D I E S O N T H E DISTRIBUTION OF DNA CONTENT OF MUCOSA CELLS IN EARLY GASTRIC CANCER H. Hyodo, J. Kobayashi, Dr. Sci., H. Nishikawa, K. Morimoto, T. Takagi, a n d S. Sako,

Department of Medical Radiology, Tokushima University School of Medicine Since the i n t r o d u c t i o n of D N A distribution in the mucosa of early gastric cancer in 1967, the study of D N A has been m a d e mostly in the s u r r o u n d i n g legion of cancer. This study has e x a m i n e d the relations between the limit of p a t t e r n of D N A in adjoining cancerous legion a n d t h e b o u n d of discolor as 24 cases of early gastric cancer, further as the possibility of biopsy. T h e distribution of D N A content per cell in mucosa cells of early gastric cancers was as similar as t h a t in the cancers. Polyploid a n d aneuploid cells were observed in all cases in the surroundings of the cancers. These regions were a b o u t from 0 to 4 cm. (1 case from 0 to 2 cm, 1 case to 3 cm, 14 cases to

4 cm, 9 cass to 6 cm.) T h e region of discolor was observed from b o r d e r l a n d of cancerous legion to 4 c m in almost cases. T h e frequency distributions of D N A c o n t e n t per nucleus in early gastric cancers a n d some gastric disease sampled by biopsy were studied by means ofmicrospectrophotometrical method. In the early a n d a d v a n c e d gastric cancers, all cases showed wider distribution of D N A content per nucleus t h a n in control distribution. T h e patterns of D N A in biopsies was similar to the general histological sampled of the sections. I t is possible to study of D N A in the gastric mucosal cells by endscopie biopsy.

(129) T H E S E R U M P R O T E I N S IN PATIENTS WITH CARCINOMA OF THE STOMACH H. T o m o d a , K. Soejima, M. Furusawa, a n d K. I n o k u c h i

2nd Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan It is well k n o w n t h a t m a n y diseases p r o d u c e a m a r k e d alteration in the level of the s e r u m protei n . T h e first report concerns the results obtained from the electrophoretic evaluation of the serum protein-levels of 397 patients with carcinoma of the stomach. As the stage of carcinoma of the s t o m a c h progresses, the albumin-level is reduced, the level of the a-globulins, especially c~2-globulin, is raised a n d there is no significant difference between the f l - a n d ~'-globulin levels a n d the stage of c a r c i n o m a of the stomach. T h e next report concerns the results o b t a i n e d from the m e a s u r e m e n t of subfractions of a globulins, a2-Antitrypsin, c~-Acidglycoprotein a n d H a p t o g l o b i n , in 38 patients with carcin o m a of the stomach a n d immunoglobulins, IgA, I g G a n d IgM, in 34 patients with carcin o m a of the s t o m a c h by single radial i m m u n o diffusion method. As the stage progresses, the level of subfractions of c~-globulins is raised a n d t h e r e is a

Proceedings of the 58th Annual Meeting, 1972--Tokyo--( H) rise in IgG-level of immunoglobulins. We think that these alterations of serum proteins in patients with carcinoma of the stomach are clinically interesting, because these changes are associated with the degree of development of carcinoma of the stomach.

(130) T H E S T U D I E S O N T H E VARIOUS KINDS OF FLUORESCENT MATERIALS FOR CANCER DETECTION R. Sassa, T. U n u m a , and T. Iwase

Department of Gastroenterology, The Institute for Adult Disease, Asahi Life Foundation. T. Yoshioka and M. Kusakabe

Toshiba Research and Development Center M. Iio

The 2nd. Dept. of Internal Medicine, Faculty of Medicine, Univ. of Tokyo. Since 1953 fluorescent materials are applied for the purpose of diagnosis of malignancy. However still many problems are remained to be solved before this method is used conventionally. Major problems are divided in two. The one is the nature of lights to be used for stimulating fluor~escent materials. And the other is the method to detect fluorescent light. In the past ultraviolet light and eye or camera detection were used. In the present study authors have introduced the use of visible light and spectrometry for this purpose. Results obtained were summarized as follows. 1) F l u o r e s c e n t s p e c t r u m : M a n y fluorescent materials using for cancer detection showed the stronger fluorescence when stimulated by visible light than by U.V. light, except Acridine Yellow. Spectrum of Fluorescence of Acriding O r a n g e (AO), F1uorescin (FR), Tetracycline (TC), Vinblastin and Actinomycin D were successfully observed by fluorescent spectrometer.

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2) B l o o d l e v e l o f f l u o r e s c e n t m a t e r i a l : When T C and A O were given to rabbit intravenously, the blood level decreased rapidly in the case of TC, but slowly in AO. 3) Shift o f s p e c t r u m to blue: When F R was administrated to the dog intravenously, the fluorescent spectrum of F R in plasma showed the shift to red in a first stage and then shifted towards blue. Finally, it showed shift to blue. 4) O r g a n d i s t r i b u t i o n o f f l u o r e s c e n t material: Organ distribution was studied for rabbit with the elapse of time. A O was uptaken rapidly, but T C was trapped slowly into the esophagus and stomach. 5) A f f i n i t y to t h e c a n c e r : T C or F R was administered to the patients with gastric cancer before surgery. T h e n the resected specimen was illuminated by U.V. light according to the published procedure, but no fluorescence was observed. A O was administrated to the patients, also. Biopsy specimen of gastric mucosa was emulsified and its fluorescent spectrum was measured. It revealed the presence of slight peak at 510 m/~ in cancer tissue, but none in the normal gastric mucosa.

(131) A C I D S E C R E T I O N IN GASTRIC CANCER: GROSS TYPE AND GASTRIC ACIDITY S. Kobayashi, M. Kizu, and T. Kasugai

Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya, Japan In order to search for the pathogenesis of developing ulceration on the surface of cancerous tissue, a relationship between the gross type, and gastric acidity and associated gastritis were investigated. Gastric analysis was performed by giving a patient either one of Histalog, 1.0mg/kg IM, Tetragast:in, 4/t/ kg I M or Pentagastrin 6/t/kg IM. Associated gastritis was interpreted on the basis of gastroscopic findings of the body mucosa. Free

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hydrochloric acid was present in two of six cases of protruded gastric cancer and mucosal atrophy was seen in all cases. Of 17 benign gastric polyps, 9 did not have hydroch!oric acid, 10 having atrophic mucosa. All three patients with atypical epithelium (ATP) demonstrated achlorhydria and atrophic mucosa. Regardless of the nature of a lesion, achlorhydria with associated atrophic gastritis predominated in protruded lesion of the stomach. Conversely, the presence of free hydrochloric acid without associated atrophic gastritis was most common in the group of depressed type of gastric cancer after stimulation. Only case with achlorhydria was noted in 41 with either IIc or IIc § like lesion, which tendency was totally similar to that in benign peptic ulcer diseases. The fact suggested that ulcerative changes on the mucosal surface of gastric cancer, more frequently in early gastric cancer, were due probably to petpic digestion of gastric juice and could show apparent healing with treatment of antacids and anticholinergics. Prior to stimulation, achlorhydria was demonstrated in 70% of all cases while in 17% after stimulation. It is concluded that ulcerative changes in malignant lesion would be most likely produced by peptic activity of gastric secretion as in benign peptic ulcer diseases. (132) CLINICAL STUDIES ON THE P R O T E I N IN THE GASTRIC J U I C E K. Yoshida, T. Kembo, T. Yoshida, Y. Suga, T. Suguro, Y. Kono, and S. Mitsui

3rd Department of Medicine, Iwate Medical University, School of Medicine, Morioka A relation between the change of the gastric mucosa and the protein content in gastric juice was studied. The subjects were 19 patients with peptic ulcer and 27 controls. The gastric juice from both groups were collected

before and after the histamine injection. The protein content in gastric juice were measured by Biuret method and identified with the method of agar immunoelectrophoresis and electrophoresis with cellulose acetate strips. Albumin, IgA and IgG were measured by electroimmunodiffusion. The following results were obtained : 1) The protein content in gastric juice decreased after the histamine injection in both groups. 2) Electrophoretic pattern of the protein by cellulose acetate electrophoresis showed 1 to 5 bands in both groups. 3) Using the method of immunoelectrophoresis, albumin, IgA and IgG were found in the gastric juice of both patients with peptic ulcer and controls. 4) By electroimmunodiffusion IgA and IgG were detectabl even in unconcentrated gastric juice. IgA was detected in the gastric juice in 4 of 13 patients with peptic ulcer and in 5 of 12 controls. IgG was detected in the gastric juice in 7 of 13 patients with peptic ulcer and in 3 of 12 controls. Mean value of IgG/IgA ratio of the gastric juice was 1.2 in 5 cases including 3 patients with peptic ulcer and 2 controls. On the contrary that of the serum was 5.9 in 15 controls.

(133) EFFECT OF DAMAGING V E N T R O M E D I A L HYPOTHALAMUS (SATIETY CENTER) ON FASTING GASTRIC SECRETION Y. Nagamachi and T. Nakamura

1st Department of Surgery, Gunma University School of Medicine, Jl,Iaebashi, Japan Goldthioglucose is capable of damaging the ventromedial hypothalamus (satiety center) and inducing obesity in dogs. Body weight was increased, significantly, in the goldthioglucose-treated dogs during an 8-week period. Daily food intake was also increased, signifi-

Proceedingsof the 58th Annum NIeeting, 1972--To.~y)--(H) candy, as high as 20% or more, in C8% of the goldthioglucose-treated dogs. The sensitivity of the fundic gland in satietycenter damaged dogs is somewhat promoted by vagal impulses during the fasting period. Fasting gastric secretion, in the satiety-center damaged and vagally innervated dog, was increased momentarily and it is difficult to maintain, accurately, such a sensitivity in the denervated dogs. In the fasting period, using the insulin or the decrease in A-glucose levels (arteriovenous glucose difference) as a warning signal, the hypothalamus may send signals automatically to the stomach via a vagal route before feeding, thus, the gastric gland may be stimulated or prepared for future digestion in step with feeding. In contrast to acid secretion, pepsin secretion is independent of the vagus and presumably controlled through humoral or other mechanisms.

(134) T R I T I A T E D T H Y M I D I N E AUTORADIOGRAPHIC STUDIES ON T H E A S T R I C M U C O S A L L E S I O N S BY U S I N G "PHYSICAL P R E S S U R E M E T H O D " H. Suto, T. Higuchi, J. Kobayashi, M. Onai, K. Isizuka, A. Takei, M. Simoda, T. Sekiguchi and K. Shichijo

First Department of Internal Medicine, School of Medicine, Gunma University Chronic gastritis, gastric atypical epithelium and gastric cancer were comparatively examined by autoradiography using 3H-thymidine. Method: Gastric mucosal samples surgically obtained from 20 cases of chronic gastritis, 2 cases of gastric atypical epithelium and 1 case of gastric cancer were examined. "physical pressure method" (in vitro), which wa devised by us, was used in labeling with 8H-s thymidine. Results: 1. C h r o n i c gastritis. In superficial gastritis, labeled cells were found

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in the foveolae and neck region of the gastric glands. The labeling index was 2.4% on the average. In hyperplastic atrophic gastritis, labeled cells were found in deeper parts of foveolae and neck region of the gastric glands with the average labeling index of 4.2%. In atrophic gastritis, labeled cells were irregularly distributed with the average labeling index of 4.9o/0. In intestinalized gastric mucosa, the deeper layers were labeled, with the index of 2.9% . II. A t y p i c a l e p i t h e l i u m . Labeled cells were compactly found toward the surface, and scarcely seen in deeper layers. The labeling indexes of 2.6 and 3.0% were obtained. III. G a s t r i c c a n c e r . Labeled cells occurred quite irregularly, with the index of 18.6%. Discussion: In atypical epithelium, different from cancer, proliferative cells were found in a definite region. The labeling index in these cases were approximately equal to that in chronic gastritis. The labeling index was considerably higher in gastric cancer than atypical epithelium and chronic gastritis.

(135) T H E C L I N I C A L S T U D Y OF UPPER GASTROINTESTINAL BLEEDING Y. Akashi, K. Mori, K. Ogasawara, R. Tanaka, K. Yoshikawa, and T. Takahashi

Department of Internal Medicine, Kyoto City Hospital A study was made of 255 cases, hospitalized with upper gastrointestinal bleeding for the past six years at Kyoto City Hosiptal. The frequency of bleeding causes was following; gastric ulcer 35.3%, duodenal ulcer 17.7, stomach cancer 14.9, esophageal varices 8,6, erosive gastritis 4.3, miscellaneous 9, undetermined 10.2 The early gastroscopy was effective in order to determine the bleeding sources and establish diagnosis without major accidents. The incidence of severe group (requiring emergency operation) in patients with gastric ulcer was

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higher than that in patients with duodenal ulcer. Respectively the mortality rate of gastric ulcer and duodenal ulcer was 2 ~o. Only those patients with severe complication died (Pneumonia, subacute hepatitis, chronic myeloid leukemia). A m o n g all the patients with gastric ulcer, the ratio of bleeding ulcer is increasing from the age group above fifty and massive bleeding occurs more frequently in patients above the age of sixty. Histological studies were made on gastrectomized material during emergency operations. In one third of them there was acute gastric ulcer, which occured mainly .in the corpus of the stomach, multiple in number for half of them, round or linear in shape. In 70% of all the collected material in emergency cases, there were arteries opening directly in the base of ulcer. The bleeding was more severe from acute gastric ulcer than from chronic gastric ulcer and early prophylactic operation for acute gastric ulcer is suggested. In some of the undetermined cases, bleeding from acute gastritis is supposed to develop.

(136) S C A N N I N G E L E C T R O N MICROSCOPIC STUDY ON THE HUMAN GASTRIC MUCOSA T. Ogata, S. Tanaka, T. Seito, H. Matsuda, T. Imajo, K. Moriyasu and Y. Takata

Dept. of Surgery, Okayama University Medical School, Okayama Samples of normal and pathological h u m a n gastric mucosa were fixed in 2.5~ glutaraldehyde, dehydrated in acetone, dried in air, coated with gold and examined under a scanning electron microscope. The surface structure of the gastric mucosa was well preserved in this process. In the pyloric glandular area, the gastric glands had a columnar structure with a deep hole in the center, namely, a "gastric pit". The deep hollows among the columnar strut-

tures were tentatively named "Cleavage or cleft" in this study. The surface mucous cells were arranged rather like a bunch of grapes and the microvilli appeared as tiny processes. Near the top of the gastric glands, small pores appeared at the apical surface of the mucous cells. In some cells these holes had fused into one large hole per cell and mucous granules were secreted through these holes. In the normal gastric glands, the size and arrangement of gastric g!ands and gastric pits were usually regular, but in chronic gastritis they were irregular. And in gastric cancer, they lose their surface structure of gastric glands, and irregular proeeces or holes had appeared on the surface.

(137) H I S T O L O G I C A L I N V E S TIGATION OF THE DIGESTIVE M U C O S A BY USE O F IMMUNOFLUORESCENT TECHNIQUE H. Kamei, H. Murai, T. Takemitsu, T. Kanemitsu, M. Ishii, M. Imaizumi, and T. Kondo

The 2nd Dept. of Surgery. Nagoya Univ. School of Med. A histological investigations were made on the digestive organs associated with various patho!ogical changes by the use of immunofluorescent staining with the rabbit antisera against the preparations of the gastric cancer cells and the mucosa of the stomach and the small intestine, respectively. Free gastric cancer cells for immunizing r~bbits were obtained by passing through the mesh with small gage after cutting with scissors the cell rich gastric cancer tissue which were obtained at surgery. The other two preparations were obtained as the supernatants in phosphate buffered solutions after the freeze thawing of the normal mucous m e m b r a n e of the stomach and the small intestines, respectively. When the three kinds of rabbit antisera were

Proceedings of the 58th Annual Meeting, 1972-- Tokyo--( H) tested by the Ouchterlony and immunoelectrophoretic techniques against human whole sera, gastric juice and the antigens used for the immunization, the presence of several precipitin lines which were mostly common in three antisera against individual tested materials, and some specific lines which were found between the anti-gastric cancer cells and the said preparation from gastric cancer tissue were found. By fluorescent technique, three antisera stained positively the certain components of the extracellular secrets and the epithelial cells of the digestive organs. They positively stained the rat digestive epithelial cells, but extra cellular secrets in slight degree. Partly different components were apparently stained by these antisera. It was greatly impressed that the specific staining pattern was found in the tissue of the digestive mucosa associated with various diseases. (138) E F F E C T S O F E X P E R I MENTAL ADMINISTRATION OF PARIETAL CELL ANTIBODY AND INTRINSIC FACTOR ANTIBODY ON RAT GASTRIC MUCOSA M. Inada

Department of Geriatrics, Faculty of Medicine, Kyoto University G. B.J. Glass

Section of Gastroenterology, New York Medical College M a n y papers have reported the presence of circulating parietal cell antibody (PCA) and intrinsic factor antibody (IFA) in patients with chronic gastritis and pernicious anemia. In this paper, animal experiments were performed to study effects of these antibodies from patients or rabbits on secretory function of acid, intrinsic factor, and pepsin and on the morphological changes; mucosal thickness, surface area, and parietal and peptic cell masses.

Ninety-six

female

Sprague-Dawley

rats

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weighing ca. 300 g were divided into 4 groups of control rats (I no injection, II saline, I I I normal human IgG, I V normal rabbit IgG) and 4 groups of experimental rats (V PCAalone, VI P C A + I F A , V I I rabbit anti-human IF, V I I rabbit anti-rat IF). Each group was composed of 12 rats and each rat was injected as IgG (4mg) saline solution into tail vein for 8-12 weeks. IgG was purified from antibody-containing sera by DEAE-cellulose column. Rat gastric juice was collected through a small tube every other week to assay acid, IF, and pepsin followed by calcuIation of hourly out-puts. Extirpated stomach opened along greater curvature was pinned out to make no mucosal folds on a card-board and was circumscribed with a pen on it. After fixation, 6 strips were cut" for preparation of sections followed by staining with toluidineblue. Glandular thickness was measured and parietal and peptic cell mass were calculated from numbers of cells exactly counted at 18 selected sites with application to a formula set up in this study. Hourly outputs of acid, IF, and pepsin in experimental groups were expressed by ~ inhibition rate (H.O. of experimental group H . O . of control group 100). Inhibition rates of V, VI, V I I , and V I I I groups showed 46.4, 53.6, 67.3, and 34.55 in acid secretion, and 27.4, 60.7, 37.8, and 27.85, in IF secretion, and 54.7, 66.0, 53.7, and 30.1}o in pepsin secretion. O n the other hand, ~ decrease rates in morphological changes w e r e as follows; the range from 49 to 75~o in thickness, and 59.2, 50.2, 68.1, and 68.4% in parietal cell mass and 67.2, 54.0 69.5, and 62.8% in peptic cell mass. These results suggested that hypofunction and decrease of numbers of parietal or peptic cells in chronic gastritis and pernicious anemia were mainly due to the reactions of these circulating antibodies.

174 (139)

Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(H) PHARMACORADIOGRAPHY O F T H E C O L O N BY METOCLOPRAMIDE SYRUP K. Ebata, N. Yamanaka, and S. Watanabe

Department of Radiology, Nihon JlIedical School Y. Yoshida and H. Mori

Department of Radiology, Izu Teishin Hospital. In principle, radiographic diagnosis of the colon should be made by the peroral method for functional changes and by the barium enema method for organic changes. However, the pharmacoradiographic technique enables satisfactory diagnosis of organic changes by the peroral method. We tried to make contrast by introducing Metoclopramide syrup orally and obtained excellent results. In 30 min. after visualizing the stomach, following the routine examination of the small intestine is performed, 20 ml. of Metoclopramide Syrup (Primperan or Eliten syrup) is orally administered to take pictures of the colon over a period of 60 to 150 min. The percentage of subjects whose colon was visualized beyond the transverse coIon within 90 min, after dosing varied greatly with the drug given: 75.5~ for Primperan syrup, 26.7% for syrup containing no metoelopramide, 70.0% for Eliten syrup, 26.7% for syrup containing no metoclopramide, 70.0% for Primperan inj., and only 8o/o, for no medication at all. In an observation 3 hrs.. The percentage of patients whose colon was visualized to the descending colon or further was 80 ~85~ for the Metoclopramide syrup group and 26% for the non-medicated group. This peroral method is considered to be applicable not only to mass survey but also to the screening of subjects for colonic changes. If air is introduced rectally at the time of contrast, the visualization of the colon may develop into a clear doublecontrast image which is almost comparable to that obtained

by the injection method. Thus this may well be a highly precise screening method. (140) C O L O N I C X - R A Y EXA M I N A T I O N BY M E A N S O F PERORAL BARIUM INTAKE METHOD S. Tsukasa, H. Sato, Y. Chuman, N. Nakahara, H. Taniguchi, S. Ehira, M. Hori, T. Irisa, and H. Yokoyama

Second Department of Internal Medicine, Kagoshima University School of Medicine The fully effective method of colonic X - r a y examination has not yet been established, though it has been improved considerably these days. We, in the course of examining 1807 cases for four years by peroral barium intake method, have come to shorten time required for the examination and to obtain better diagnostic accuracy by improving the examination procedure and technology. The former method has a drawback in taking long time for the examination. On the other hand, it has an advantage that stomach, small and large intestines can be examined in succession in a same day and that normal and physiological barium passage through intestines can be observed as well. We used Metochlopromide (to be given intramascularly) and D-sorbit for the purpose of cutting time needed for the examination short to obtain better result. In 63% of the cases examined, the examination was completed within three hours while 93~o was finished within five hours. Polyp cases, especially colonic, were studied in connection with diagnostic accuracy. Double-contrast X - r a y examination of sigmoid and rectum was performed by infusing barium into them through anus and, as a result, better diagnostic accuracy was obtained. Thirty-two colonic polyps were found in 22 cases by single peroral barium intake examination. Ten out of 26 polyp-suspected cases were given definite diagnosis while the other 16 were proved that they had been given false diagnosis by

Proceedings of the 58th Annual Meeting, 1972-- Tokyo--( H ) means of barium enema method and colonic fiberscopy. There were i0 polyps, the sizes of which were less than 10 m m in diameter, overlooked in 7 cases. Considering that high incidence of cancer has been seen in the lesions, the sizes of which are more than 10 m m in diameter, it may be concluded that colonic cancer in early stage can be detected by the improved method. It has been considered, judging from the fact that many polyp patients without being accompanied by any subjective signs and symptoms have been found, that establishment of more accurate and less painful routine X ray examination method which will enable us to examine and find m a n y colonic polyp patients in a short hour is required. "Premedication" and barium concentration are the subjects to be investigated further for the purpose of bettr diagnostic accuracy of the improved method.

(141) O N T H E N O R M A L R O E N T GENOGRAPHIC PICTURE IN THE BARIUM ENEMA (ON T H E H I G H P O S I T I O N OF THE SPLENIC FLEXURE) T. Kunieda and Y. Ogushi

Department of Radiology, School of Medicine, Gifu University The criteria on the normal roentgenographic picture concerned with the course, the position, and the angulation of the colon, is not defined. But Hayashida et al. indicated the criteria on the normal roentgenographic picture of the colon. We doubted on the category, that is to say the normal position of the splenic flexture is in 5 to 10 centimeter from the diaphragm in the patient upright and expiratory phase. Therefore, we divided 99 cases into three groups by using Hayashidas criteria, namely a group of the normal positon of the splenic flexture, a group of the high position of the splenic flexture, a group of the high position and the abnormal angulation of the splenic

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flexture, and investigated them from the subjective symptom. It was suggested by our study that there was no significant difference amidst three groups. (142) H I S T O C H E M I C A L S T U D Y O F THE TRUE CHOLINESTERASE (CHE) A C T I V I T Y I N T H E COLONIC MUCOSA K. Kawakami, M. Kuroda, M. Kuroda, D. Sasaki, S. S6ma S. Yanagiya, A. Munakata, and F. Matsunaga

The 1st Department of Internal Medicine, Hirosaki Universty School of Medicine, Hirosaki,

Japan The true eholinesterase (ChE) activity of the colon mucosa was histochemically (after Karnovsky) assayed in the materials obtained by biopsy with Colonofiberscope in various colonic diseases. ChE activity was higher in irritable colon syndrome than in colon organic diseases, such as cancer of the colon, polyp of the colon, ulcerative colitis and the others. ChE activity and stoolanomality had no significant correlation to each other. In irritable colon syndrome almost all cases with P type (hyposympathicotonia) in mecholyl test showed a high ChE activity. A half cases with N type (normal) also showed a high activity. From the above results it was concluded that measurement of ChE activity in the mucosa was valuable to differenciate functional colon disease from colon organic disease, and for etiological diagnosis of irritable colon syndrome.

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176 (143)

CLINICAL EXPERIENCE OF INTESTINAL ENDOMETRIOSIS M. Abiko

The Second Hospital of Tokyo Women's Medical College, Department of Internal Medicine H. O h u c h i

Department of Gynecology Intestinal endometriosis is one of the causes of bowel m o v e m e n t disorders. But it is not p o p u l a r even a m o n g the doctors. I have experienced the 6 cases. T h e characteristic s y m p t o m s are constipation, rectal or gluteal pain, dysmenorrhoea a n d rectal pain by coitus. Constipation is noted in 2 of 6 patients, a n d increased passages are only in one. However, in 4 of 6, passages were increased d u r i n g the m e n s t r u a l period. Sterility is n o t e d only in 2 of 6. O n e p a t i e n t h a d melena. X - r a y examinations were carried in 4, a n d colonoscopy examinations, in 2. By the b a r i u m e n e m a study, filling defects were observed in 3, a n d niche or adhesive changes were in 4. By the colonoscopy, in one of two, s u b m u cosal t u m o r s a n d mueosal bleeding were observed.

of O K A Y A M A univrsity hospital a n d the municipal hospital H I R O S H I M A between 1962 a n d 1971, a b o u t 50% came to surgical t r e a t m e n t involving colonic resection, in w h i c h 10 patients were all with severe attacks a n d their clinical laboratory data showed the critical n u m b e r , score 3 or more. T o seven patients of them, u r g e n t operation as a n elective measure was applied a n d true emergency surgery was r e q u i r e d for the rest of t h e m in w h i c h a n elder p a t i e n t of high risk lost his life shortly after surgery. I n the course of conservative t r e a t m e n t , two cases showing the score 3 or more h a d lost their lives as the result of delay a n d i n a d e q u a t e m a n a g e m e n t . T h e majority of mild or moderately severe attacks of ulcerative colitis, w h i c h h a d subsided with conservative m a n a g e m e n t , were retrospectively scored according to the critical n u m b e r calculation a n d t u r n e d out to be the score 2 or less. Deliverating u p o n these data, we h a v e proposed the critical n u m b e r (score 3) of this disease, indicating the u r g e n t operation required. A severe attack of ulcerative colitis with the score 3 or more is consequently a medical e m e r g e n c y a n d should be t r e a t e d as urgent surgical condition, instituting intensive course of conservative measure.

(145)

ON TUBERCULOSIS OF THE COLON K. Yukawa, et al.

(144) I N D I C A T I O N S F O R U R G E N T SURGERY IN THE TREATMENT OF SEVERE ULCERATIVE COLITIS; SPECIAL REFERENCES TO THE CRITICAL NUMBER OF THIS DISEASE C. Tai, T. K a w a s h i m a , W. Oosawa, H. Asakura, H. Senba, a n d T. H a t a y a m a

Department of Surgery, Okayama University Medical School and Department of Surgery, Hiroshima Municipal Hospital I n a series of 42 patients with ulcerative colitis seen by us at the 1st surgical d e p a r t m e n t

Yukawa Gastroenterological Hospital, Osaka

Summary (1) Discussions were held on b o t h roentgenographic a n d pathological examinations of four cases of colonic tuberculosis. A m o n g w h i c h three cases were surgically operated. (2) I n two cases of t u m o r form, the typical hour-glass shape was not seen in roentgenograms, t h a t is one edge of the focus showed like a n apple-core. (3) I n two cases of ulcerative form, lesions were roentgenologically mosaic in p a t t e r n and, were skipping, so t h a t they were, at first sight t h o u g h t to be C r o h n ' s disease of the colon. I n

Proceedingsof the 58th Annual Meeting, 1972-- Tokyo-- (H) making a diagnosis, biopsy was thought to be most important. So, as a next step, a diagnosis was made from biopsic specimens by using romanoscopy or fiberscopy. As the result, tuberculous granuloma with central necrosis was found. And that was taken from ulcer base and not from multiple pseudopolipoids.

(146)

C H A N G E S IN P O R T A L A N D INTRALUMINAL SEROTONIN LEVELS FOLLOWING INSTILLATION OF HYPERTONIC GLUCOSE SOLUTION IN T H E P R O X I M A L S M A L L INTESTINE

T. Konishi, M. Miyata, H. Shimazu, T. Kinoshita, K. Nukada, and T. Yamagishi

First Department of Surgery, School of Medicine, University of Tokyo It is well known that portal serotonin level increases significantly after instillation of hyprtonic glucose solution in the proximal small intestine in experimental animals. However, the exact mechanism of this augmentation of portal venous serotonin is not necessarily demonstrated. The present study was carried out to investigate this mechanism in anesthetized dogs. After instillation of 50~o glucose, there was a prompt increase in portal serotonin concentration which reached the peak at 10 minutes, maintaining the level for 20 minutes, and then gradually decreased. Similar changes occured after instillation of 8% NaC1 although the magnitude was comparatively small. No significant alteration of portal serotonin concentration was noted in case of 50% glucose load following exposure to 2~ lidocaine. Introduction of 50% glucose caused a progressive increase in intraluminal serotonin concentration till 60 minutes. Similar changes occured after instillation of 50 ~o glucose following exposure to 2% lidocaine although the magnitude was comparatively small. In case of 8~o NaC1 load, however, intraluminal sero-

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tonin concentration reached the peak at 30 minutes but then gradually decreased. These data failed to show close correlation between portal and intraluminal serotonin levels. O n the other hand, there occured much greater increase in portal serotonin level after instillation of serotonin in saline than after that of salin alone. Our data would suggest that intraluminal serotonin might play in part a role in the mechanism of increase in portal serotonin level after intraluminal hypertonic glucose load. (147) S T U D I E S O N P E N E T R A T I O N O F ACTIVE POLYPEPTIDES THROUGH I N T E S T I N A L M E M B R A N E (V) --HISTO-PATHOLOGICAL CHANGE OF INTESTINAL BRUSH BORDER CELL-K. Harada, S. Nakano, T. Yoshioka, and T. Sakai

Department of Physiology, The Jikei University School of Medicine, Tokyo In the last 57th General Assembly of J a p anese Society of Gastroenterology 1971, our report on penetration phenomena of glucose, insulin and tryptophane through intestinal wall was presented, the data of which were obtained by use of everted intestine of rats treated with N a O H , CHsCOCH3, HC1 etc., and analyzed rom the view of patho-physiology. This time histo-pathological investigation of intestinal brush border cell in relation to above experiments and further obtained results on penetrating conditions of materials are presented. When the time length of treatment with above agents is within 10-60 see or over 10 min, the values obtained are unstable and characteristic features of active transport which have been confirmed by our own method, are not found. In 2-5 min's treatment with 0.1N N a O H , however, insulin penetration is enhanced, and transport of tryptophane and glucose is inhibitory, which might suggest that there must exist synergistic action be-

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tween insulin and glucose or between tryptophane and glucose for active transport. O n the contrary, in treatment with such degenerative agent of cellular lipids structure as 10% C H 8 COCH3, no characteristic features of active transport was olzserved. In treatment with 0.1N H C I each transport of insulin, tryptophane and glucose is inhibitory, which might suggest that transport mechanism of intestinal m e m b r a n e cell could be disturbed. As the results it will be considered that selective structural change of such the components of intestinal brush border cell membrane as protein layer, lipid layer, mucopolysaccharid covered over cell membrane, could produce their own features in transport which are different one another, and the present problem will be also of pathophysiological interest.

(148) E F F E C T S O F H U M A N INTESTINAL FLORA ON THE BILIRUBIN AND BILE ACIDS METABOLISM K. Shindo, K. Fukushima, S. Odagiri, K. Tarao, Y. Saito, K. Ohara, and S. Sasaki

The First Department of Internal Medicine, Yokohama City University Medical School In oder to study the influence of h u m a n intestinal bacteria on bilirubin and bile acids metabolism, the conversion of bilirubin into the other metabolites and the splitting of conjugated bile acids by intestinal microorganisms were investigated by column chromatography and thin layer chromatography. All to the species tested metabolized bilirubin but not all of their strains. The percentages of the metabolizing strains in each species differed from 75% t o 2 8 % . Corynebacterium. enterococcus, aerobacter and bacteroides had higher percentages. The percentages of the strains which metabolized to urobilinogen were highest (8%) in enterococcus and aerobacter, lower in intermediate coliform bacillus

and Escherichia coli, and none in the other species. Species of which all of the strains splitted conjugated bile acids were enterococcus, bacteroides and corynebacterium, and most of the strains splitted were staphylococcus epidermidis and lactobacillus bifidus. Species of which none of the strains splitted were Escherichia, lactobacilli except lactobacillus bifidus, staphylococcus aureus, aerobacter, pseudomonus, candida, and veillonella, and almost none of the species splitted was intermediate coliform. C o n c l u s i o n : O f all the species tested various percentages of their strains metabolized bilirubin in various degrees. All or none, or almost all or none, of the strains of each species tested splitted conjugated bile acids, and it is probable that the presence or absence of this ability would be a proper character of each species.

(149) A M I N O A C I D D E C O M P O S I T I O N BY L. B I F I D U S A N D L. A C I D O P H I L U S T. Tomoda, N. Kaneda, H. Yamaguchi, and T. Hayashi

Department of Clinical Pathology, Osaka Medical College T. Tanaka

Pharmaceutical Research Institute M a n y experiments on amine production of aerobic and anaerobic intestinal bacteria have been studied in the previous reports. In this study, amino acid metabolism of lactobacillus bifidus and lactobacillus acidophilus was examined. L. bifidus was isolated from not only the feces of children but also that of adults. But in each case of the adults, the variation of the quantity was remarkable. Amino acid component of L. bifidus and other intestinal bacteria was compared. Alanine, cystine and valine were more than the other microorganisms but these differences were not specially, amino acid consumption in filtrate of culture medium which L. bifidus and L. acid.

Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(H) have grown, was examined. M a n y amino acids were consumed in L. bifidus than L. acid. and was not always in parallel with amino acid decarboxylase activity. Ornithine, lysine, histidine, glutamic acid, tyrosine and phenylalanine decarboxylase activity was examined for L. bifidus and L. acid. The production of some amines such as cadaverine, histamine and tyramine was recognized in a few strains of these species, but little quantity. The change of tyrosine decarboxylase activity of L. bifidus by successive cultivation, was examined. Tyrosine decarboxylase activity decreased by successive cultivation. O n the other hand, in other microorganisms (Klebsiella, P. vulgaris and St. faecalis), the activity did not change. Sensitivity for various antibiotics of L. acid. and L. bifidus showed same pattern, but differed from other intestinal bacteria. It was demonstrated that amine production of L. bifidus and L. acid. was rare and unstable. From this viewpoint, the existence of these strains will be also useful for body. 1) 2)

Literatures Tomoda, T and T a n a k a T : The Japanese Journal of Gastroenterology, 67: 4, 1970. Tomoda, T et .al: T h e Japanese Journal of Gastroenterology, 68: 1167, 1971.

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INTESTINAL ION TRANSPORT IN RAT 1) P O T A S S I U M T R A N S P O R T A T SODIUM EQUILIBRIUM CONCENTRATION 2) E F F E C T O F G L U C O S E A N D PITRESSIN ON WATER, SODIUM AND POTASSIUM TRANSPORT J. Suzuki, Y. Kofune, A. Urase, A. Yamagata, N. Sugino, M. Hatano, and K. Oshima.

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potassium transport of isotonic solution in jejunum, ileum and colon of anesthetized rat at sodium equilibrium concentration were determined and effect of glucose and pitressin on water, Na and K transport were observed. Male wister rats weighing 200 to 300 g were anesthetized with Nembutal (5 mg per 100 g). The abdomen was opened with midline incision and 15 cm of intestine was isolated in vivo with care to preserve normal blood supply. The segment of intestine was cannulated at both ends with silicon tubes. The composition of perfuson solution was NaC1 120-140, KCI 5, MgC12 1.5, CaC12 4, NaHCO8 20 m M / L and were kept isotonic by addition of mannitol. K efflux was determined from the changes of total radioactivity of 42KC1. Water efflux was determined from the changes of phenol red concentration. Electrical potential difference between the mucosal and serosal surface was measured with a pair of Calomel electrodes using a Keithley Model 610C electrometer. An indirect electrode was placed on the serosal surface. Mainly, K was absorbed passively in intestine and K absorption was largest in the jejunum and in ileum larger than in colon. Na absorption and K secretion was, in great part, active component and largest in the colon and larger in ileum than jejunum. Water absorption was apparently passive, depending upon Na movement. (151) A S I G N I F I C A N C E O F S T E N O S I S OF THE PAPILLA OF VATER IN A RELATIONSHIP BETWEEN CHOLELITHIASIS AND PANCREAS --A CLINICOPATHOLOGIC STUDY-T. Tanabe, M. Ohto, and K. Okuda

Department of Internal Medicine, Nikon University School of Medicine, Tokyo, Japan

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

In an attempt to clarify ion transport by rat intestine, using stop flow perfusion technique,

The papilla of Vater is closely related to the biliary tract and the pancreas because of their

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anatomical structure. In this report, the relationship between cholelitiasis and pancreatiffs with or withont stenosis of the papilla is studied from clinical observations of 108 cases including 48 cases of cholelithiasis and from histological observations of 67 autopsy materials including 28 cases of cholelithiasis. T h e results are as follows: l) Cholangiograms with dilatation above 13 m m of the extrahepatic biliary passages have a stenosis of the papilla. The cases of cholelithiasis accompanying acute pancretitis frequently show this cholangiographic picture. 2) The ratio of the abnormal cases of cholelithiasis with stenosis of the papilla by Pancreozymin-Secretin Test shows higher than those without stenosis of the papilla. 3) A fibrosis and round cell infiltration were markedly seen at the papilla with cholelithiasis. 4) At the head of the pancreas with cholelithiasis, periductal fibrosis, cell infiltration, ductal proliferation and the tall hypertrophied ductal epithelium were observed more frequent than those at the other part of the pancreas. 5) The cases who have chronic papillitis frequently show chronic inflammatory changes at the pancreatic ducts. O n the basis of these observations, it is supported that stenosis of the papilla has an important role on the pathogenesis of a pancreatitis related to cholelithiasis. (152) T H E C H A N G E S O F T H E DUODENAL PAPILLA ON THE DISEASES OF THE NEIGHBOURING ORGANS E. Mitani, S. Yamamoto, K. Kobayashi, T. Ono, T. Kamata, S. Mohri, H. Makiishi, A. Kitano, Y. Suga, S. Tatumi, S. Mizuno, and K. Tsumori

Medicine, Osaka City University Medical School, Osaka, Japan. Department of Internal

Two hundred and thirty two endoscopic observations of the duodenal papilla were m a d e from:July, 1970 to February, 1972. W.e have studied about the changes of the duodenal papilla on the diseases of the biliary tract and pancreatic diseases. The purposes of this paper are to discuss the changes of the duodenal papilla on the various diseases of digestive tract (Diseases of the biliary tract, liver and pancreas, duodenal ulcer.) The results were as follows: (I) The size of the duodenal papilla on the diseases of the biliary tract was 17.34-2.9 m m in longitudinal diameter and 12.14-2.4 m m in transverse diameter. It became about three times as large as that of normal one. (2) In the diseases of the biliary tract the duodenal papilla, which showed type D was 64%. By endoscopic pancreatocholangiography, dilatation of the terminal part of the common bile duct was observed in the cases which papilla showed type D and D'. (3) Commonly, the size of the duodenal papilla on the diseases of pancreas did not so swell, except the case which infiltration of cancer of the pancreas extend to the ampulla of the duodenal papilla. (4) In the duodenitis (17 cases,) the cases which anatomical papilla were swelling was 47%. We believed that the inflammatory stenosis of the terminal part of the common bile duct sometimes occurred due to extension of the inflammation of the duodenum. (5) In 16 cases on the diseases of the liver, the size of the duodenal papilla was almost the same as that on normal one. (6) The swelling duodenal papilla may occur keeping jaundice and high level of A l k - - P and LAP. (153) C L I N I C A L S T U D Y F O R INTESTINAL PERFORATION T. Shimizu, K. Nomatsu, H. Hiratsuka, and M. Ichinose

Surg., Ohita Red Cross Hospital During 11 yrs. and 9 months from Jan. 1960 to Sept. 1971, we have experienced of 46 cases

Proceedings of the 58th Annual Meeting, 1972--Tokyo--(H) of intestinal perforation (33 cases of duodenal ulcer, 18 cases of trauma, 7 cases of ileus, 3 cases of intestinal phlegmon and 3 cases of foreign bodies). 54 cases were male and 10 cases were female 2 cases were under the age of 20 years, 22 cases the age 21 to 40 years, 27 cases the age 41 to 60 years and 13 cases over the age of 60 years. Operative mortality rate for intestinal perforated cases was 25% ( 16 cases out of 64 cases). The causes of death about 9 cases (56.2%) were uremia and 7 cases (43.8%) were heart failure. About the number of deaths 7 cases (43.7%) were over the age of 60 years and 13 cases (81.2o/o) were treated surgically from the onset of perforation over 24 hours. The prognosis of the pt. with perforated duodenal ulcer was favorable (mortality rate was 9%), on the contrary, the prognosis of the pt. with intestinal perforation caused by ileus was grave (mortality rate was 85.7%). By our experience the prognosis of the pt. with intestinal perforation is dominated, if early and suitable surgical treatment (especially, primary gastric resection for the perforation of duodenal ulcer) is performed. (154) S T U D Y O N C H O L E R A ENTERITIS-RADIOLOGICAL, IMMUNOLOGICAL AND BIOPSY FINDINGS

The present studies were performed on the patients of both sexes admitted to San Lazaro Hospital (Manila). The culture of rectal swabs of these patients were all positive for Vibrio eholerae. Serum albumin, globulin and immunoglobulin concentration of fourteen cholera patient was assessed by electrophoretic, immunoelectrophoretic and immunodiffusion methods and compared with those of seven control individuals. An apparent elevation of IgG and T-globulin and an decrease in albumin were observed in cholera patients. Immunoglobulin levels of the small intestinal fluids were evaluated in cholera patients as well as the control, to reveal a definite increase in IgA in the former. IgG and I g M were hardly detectable in the cholera cases. X - r a y findings of the small intestine in cholera patients revealed a marked hypersecretion and hyperkinetic peristaltsis. Histologic study of the jejunal biopsy specimens from 5 cholera cases demonstrated denudation, necrosis and degenerative changes of mucosal epithelium. A b u n d a n t mucus was found in the lumens of the crypts. The intestinal villi were coated with desquamated epithelium as well as mucus. It is surmised that rice watery stool is due to multiple focal denudation and necrosis of intestinal epithelium as well as hypersecretion of epithelial cells and excess production of mucus in the crypts.

H. Asakura, T. Morishita, A. Morita, S. Matsuzaki, M. Oda, K. Kamegaya, M. Tuchiya, and K. Sambe

(155) C L I N I C A L S T U D I E S O N INTESTINAL DISEASES A C C O M P A N I E D BY DIARRHEA

Department of Internal Medicine (Director K. Sambe), School of Medicine, Keio University

Y. Murakami, A. Machii, Y. Nitta, Y. Aiso, N. Kitahara, M. Sato, Y. Yoshizawa, and Y. Hishinuma

Cholera is characterized by severe diarrhea with fluid and electrolyte depletion. Its prevaIence has been reported in Asia and Africa. Clinical and pathological studies of cholera were carried out in order to clarify the pathogertesis of voluminous diarrhea. Methods and Results:

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Dept. of Int. Med., Tokyo Metropolitan Toshima Hospital H. Nagasako and Y. Nao

Institute of Gastroenterology, Tokyo Women's Medical College Out of total of 37,079 patients who visited our clinic during 1967--1971. 1,421 (3.8%)

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had diarrhea as chief complaint. O f them, patients of acute diarrhea totaled 1,116. 784 cases of them were subjected to stool culture examination and 125 (15.9%) were positive for pathogens, which included bacillary dysentery 32, Salmonella enteritis 28, pathological colibacillus enteritis 2 and Vibrio enteritis 63. Non-infectious types consisted of 990 of acute enteritis in which no pathogens were demonstrated and one allergic enteritis. Chronic diarrhea totaled 306, of which 80 were examined by stool culture but none were found positive for pathogens. One patient of amebic dysentery was the only infectious type: S M O N was observed in 5 patients. Others consisted of chronic gastroenteritis 80, ulcerative colitis 29, irritable colon synddrome 167, intestinal neoplasma 6 and other diseases such as valvular disease or malabsorption syndrome 17. Pathgens were demonstrated in higher percentage in patients with higher body temperature and mucous stool. However, they w e r e also found in 5-13.9~ of those with body temperature below 36~ and whose stools were watery. O n endoscopic examination, hyperemia, bleeding, ulcer and edema were observed in bacillary dysentery, acute enteritis, amebic dysentery and ulcerative colitis. In addition to these, pseudopolyp was also observed in ulcerative colitis. In bacillary dysentery, lesion was marked along the area as far as 20 cm from the anus. Intestinal atrophy was observed frequently in irritable colon. O n biopsy, there were observed hyperemia, bleeding, ulcer, edema and infiltration of inflammatory cells in bacillary dysentery, acute enteritis and ulcerative colitis. Cryptabscess was found only in one case of ulcerative colitis, which was fewer then in operated or autopsy cases.

(156) E X P E R I M E N T A L A N D CLINICAL EVALUATION OF ENDOSCOPIC PANCREATOGRAPHY H. Harada, K. Mishima, Y. Yama-

gata, M. Mandai, Y. Kondo, and Y. Uchida,

Okayama Unicersity Medical School S. Takizawa and S. Kinoshita

Mizushima Daiichi Hospital Importance of duodenofiberscope and endoscopic pancreatography and cholangiography for the diagnosis of diseases of the pancreas and papilla of Vater was evaluated on the basis of the results of 320 cases of duodenofiberscope and 167 cases of endoscopic pancreatography and cholangiography which has been performed at our institute. Followings are our results. (1) Dogs were used to evaluate the effect of volume and infusion pressure of contrast medium on the pancreatogram. Infusion of 0.5ml of60% Urographin with .0,2 atmospheric pressure was most suitable to obtain a fine pancreatogram without artefacts. (2) In man, infusion of 4 4 5 ml of medium with 0,2 atmospheric pressure was most suitable. Excessive volume or infusion pressure resulted in artefacts, so that infusion pressure and volume of contrast medium should be standardized to evaluate the endoscopic pancreatography. As a base line, we have adopted 5 ml volume and the lowest infusion pressure which enables instilment of the medium. (3) Our cases include 8 cases of cancer of the papilla of Vater, 5 cases of the pancreas cancer, 6 cases of chronic pancreatitis with calcification and lithiasis, and 12 cases of chronic pancreatitis without calcification and lithiasis. (4) Endoscopic observation, biopsy and endoscopic pancreatography and cholangiography have proved indispensable for the diagnosis of cancer of the pancreas and the papilla of Vater. (5) In chronic pancreatitis with calcification and litiasis, abnormality of endoscopic pancreatography was often remarkable (80100%), including irregularity of course, caliber and border of the pancreatic ducts and ductules. In these cases, pancreozyminsecretin test also showed remarkable abnorrmality; a decrease of all 3 factors (volume, amylase output, and max. HCOa concentration).

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(6) In chronic pancreatitis without calcification and lithiasis, in contrast, irregularity of border of the pancreatic ducts and irregular opacification of the acinus and parenchyma of the pancreas were observed in 50% of cases In these cases, amylase in the serum and urine was elevated and pancreozymin-secretin tests showed only mild abnormality such as a minimal decrease of only one factor; usually a decrease of mzx. H C O j concentration or amylase output. Thus, chronic pancreatitis should be evaluated in the basis of clinical findings, other morphological and functional tests as well as endoscopic pancreatography.

and obstruction. Radiologically, the differentiation of these two groups is now difficult. From the variation of the serum-amylase after the pancreatography, the different pattern was not recognized in these two groups. According to the above-mentioned data, no correlation of the morphological findings of the pancreatography with exocrine secretory function of the pancreas was recognized. In future, the full functional test and the biopsy of the pancreas will be studied, and it will be desirable to establish the abnormal findings of the pancreatography in the pancreas-diseases.

(157) S T U D I E S O N T H E E N D O S C O P I C A L PANCREATOGRAPHY AND PANCREATIC FUNCTION

(158) E N D O S C O P I C PANCREATOCHOLANGIOGRAPHY

T. Kurihara, K. Sakumoto, H. Okamoto, S. Sakurai, S. Ishitobi, H. Tanaka, and K. Ishihara

--COMPARISON WITH OTHER CLINICAL EXAMINATIONS--

2nd Dept. of Internal Medicine, Tottori Univ.

1st Department of Internal Medicine, Aichi Cancer Center Hospital

The pancreatic duct would be affected by the pathologic change of the pancreas. U p to date, endoscopical pancreatography is the best way to know the pathologic findings of the pancreatic duct. And then, comparison of morphological findings of the pancreatic duct obtained by the duodenofiberscopy with the pancreozymin-secretin test was studied in this report. In the normal group of the P-S test, the diameter of the main pancreatic duct was on average 3.8 m m at the head, 3.2 m m at the corpus and 1.8 m m at the tail of the pancreas. O n the other hand the prominent acknowledgement was not obtained from the view of the diameter of the main pancreatic duct in the abnormal group with the P - S test. The following findings of the pancreatic duct were studied in the above-mentioned two groups. T h a t is, flexion, irregular wall of the duct, localized change of the diameter of the duct

We have succeeded in Endoscopic Pancreatocholangiography (EPCG) in 240 cases until February, 1972. In this work, E P C G findings were compared with those of other clinical examinations. 1) Comparison with routine cholangiography: Eleven cases of gallstone, 2 of gallbladder cancer and 2 of common bile duct cancer, which were not diagnosed by routine examinations, were revealed by EPCG. 2) Comparison with pancreatic function test: Findings of chronic pancreatitis by the criteria for E P C G diagnosis of chronic pancreatitis, were obtained in 15 of 16 cases, which were normal by observation of urinary amylase for a week, and in 12 of 13 cases, which were abnormal. 3) Comparison with pancreatic scintigram: Sixteen cases of chronic pancreatitis and one of pancreatic tail cancer were found in 22 cases interpreted as normal by pancreatic

N. Kuno, T. Kasugai, I. Aoki, and M. Kizu

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scintigram. 4) Comparison with U G I X-ray and gastroscopic examinations : Two cases of pancreatic head cancer, 3 of tail cancer and 2 of gallbladder cancer were found on EPCG in 36 cases, in which extragastric pressure was demonstrated by a routine U G I examination. Two cases of pancreatic head cancer, one of tail cancer and one of gallbladder cancer with normal hypotonic duodenograms, were revealed by EPCG. 5) Comparison with duodenoscopic findings of papillary area : By duodenoscopic examination, inflammation and swelling of plica longitudinaris duodeni were twice found in cases of chronic pancreatitis and biliary diseases diagnosed by EPCG. 6) Good correlation was found between EPCG and angiography. (159) S T U D I E S ON T H E CORR E L A T I O N BETWEEN T H E R E S U L T S OF E N D O S C O P I C P A N C R E A T O G R A P H Y AND PANCREOZYMIN SECRETIN TEST S. Nakano, T. Suzuki, Y. Horiguchi, K. Kitamura, M. Miwa, K. Okada, and T. Takeda

2rid Clinic of Internal Medicine (Department of Gastroenterology) Ogaki Municipal Hospital Ogaki, Japan To confirm the abnormal findings in E.P. C.G. (endoscopic pancreatocholangiography), function test of the exocrine pancreas by pancreozymin secretin test was carried out on the same patients and compared with each other. Methods and Materials Endoscopic pancreatography was carried out on 86 patients who have hospitalized for biliary and pancreatic impairment and pancreozymin secretin test was also done on 61 of them.

Results Judging from three parameters (total volume after secretin administration, maximal bicarbonate concentration and total amylase output after pancreozymin administration) in pancreozymin secretin test, the function of the patients whose diameter of the main pancreatic duct was over 4.0 mm had showed more abnormalities. As the signs of the pancreatic impairments Hess, W. pointed out tortuosities and distortions of the pancreatic duct, irregularities of caliber, pseudodiverticula, filling of side branches and parenchymal reflexes besides dilatation of the main pancreatic duct. Correlation between these abnormal findings in the pancreatography and the results of pancreatic function, pancreozymin secretin test and glucose tolerance test, was analysed and compared. In the cases, observed abnormal findings in the pancreatography, abnormal function was detected more often (PS test 69%, G T T 78%) than another cases (PS test 42%, G T T 43%). On the other hand, remarkable abnormal function was observed in some patients whose pancreatography were quite normal. Although there are no straight relationship between both morphologic and function test, remarkable morphologic changes are apt to accompany abnormal function of the pancreas. Thus, there are some discrepancy between both tests, non-time consuming pancreatography should be added for the diagnosis of the pancreatic disorder.

(160) S T U D I E S O N T H E DIAGNOSIS OF M A L I G N A N T PANCREAT I C T U M O R S BY H Y P O T O N I C D U O D E N O G R A P H Y AND D U O D E N O FIBERSCOPY Y. Endo. M. Tatsuta. T. Morii. S. Okuda, and H. Tamura.

Centerfor Adult Diseases For these 2 years, 20 cases of pancreatic malignant tumor were diagnosed by hypo-

Proceedings of the 58th Annual Meeting, 1972-- Tokyo--( H ) tonic duodenography (HDG) and duodenofiberscopy (FDS) and proved by operation or necropsy. The radical operations were performed in 9 cases (45%). As this ratio is higher than other reports, to get some crew of earlier and more certain diagnosis, the findings of HDG & FDS in the 20 cases were reviewed in detail. 1) Findings of C-loop by HDG: enlargement, narrowing, non-symmetric findings were seen in about 50%, and abnormal findings of median wall were seen in about 65%. Swelling or deformity Of papilla vateri were in about 85%. 2) By FDS, about half of 12 pancreatic head cancer cases were definitely diagnosed. The findings were coml~ressed form, submucos~ti tumor, ulcerative change and so on. The other half also showed some change in the descending part of duodenum including papilla vateri, but indefinitive to judge malignant. 3) Cytology: Eight positive cases were obtained out of 11 cases in direct absorption cytology from pancreatic duct. This is indispensable for certain diagnosis. 4) Pancreatic ductography: In 13 "~performed cases~ 6 were determined malignant by this method, and at least some abnormal signs were recognized in all of the 13 cases. (161) CONSTANT SECRETIN INFUSION W I T H PANCREOZYMIN P R E T R E A T M E N T AS THE PANCREATIC F U N C T I O N TEST K. Fukuda, K. Sato, K. Koizumi T. Takebe, and S. Yamagata

Prof. S. Yamagata's Department of Int. Med. Tohoku University School of Medicine, 1-1 Seiryomachi Sendai, Japan The standard single injection secretin test is now accepted as the most reliable test of excretory function of pancreas, however, for large variance coefficient found in both volume and amylase output found in normal control, the method has inherent problem in detection of minor changes of the pancreatic dysfunction. Therefore, an attempt

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is made to introduce another method where pancreozymin pretreatment was given. In normal human control group, constant infusion of secretin (Boots) in dose of 1/50u. /kg/min. was done for 90 minutes after giving pancreozymin (Boots) lu./kg intravenously. Duodenal juice was collected fractionately in each 10 minutes for 90 minutes and volume, bicarbonate concentration and amylase activity were measured in each fraction and following results were obtained. 1) Volume and bicarbonate concentration reached certain plateau after 50 minu-~ tei of infusion probably reflecting the plateau of the effective secretin level in ~this period. The coefficient of variation-of both volume and bicarbonate concentration in this period and total amylase output, showed significant decrease than the results obtained by stafldard method,, although a temporaly increase of amylase concentration and volume was oh-" served shortly after pancreozymin injection. 2) The effect of pancreozymin injectior~ is short lived. Volume output and increase of icterus index of the juice was only Observed in the initial one or two 10 minutes.fractions. Therefore the separation of bile and pancreatic juice is now feasible if samples of fourth and therafter fraction periods were to be analyzed. It is, therefore, concluded that the new technic will increase the reliability and diagnostic ability of the secretin test. (162) CHANGES OF SOME ELECTROLYTES IN DUODENAL ASPIRATE, PANCREATIC J U I C E AND BILE BY S T I M U L A T I O N OF PANCREOZYMIN AND SECRETIN S. Noda, Y. Toda, T. Hayakawa, S. Nakajima, and S. Hitokawa

2nd Department of Internal Medicine, Nagoya University School of Medicine S. Nakano, T. Suzuki, and T. Takeda

2nd Department of Internal Medicine, Ogaki Municipal Hospital Some electrolytes in the duodenal aspirate, pancreatic juice and bile obtained by the stimulation of pancreozymin and secretin

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were determined on 90 subjects including controls (16 cases), diseases of biliary tract (28 cases) and pancreatic diseases (46 cases). Results were as follows: 1) The concentration of sodium ion was elevated just after the stimulation of pancreozymin and maintained almost constant throughout the course of PancreozyrninSecretin Test. The concentration of potassium was decreased after the stimulation of pancreozymin and kept constant thereafter. The lower concentration of sodium and the higher that of potassium before the stimulation were secondary to the contamination of the gastric juice and the bile. 2) In the hepatic bile from the external fistula, the ionic concentration of chloride was extremely higher than that of bicarbonate and decreased gradually after the stimulation of secretin. Changes of these anions in the duodenal aspirate were thought to be considerably influenced by the contamination of the bile. 3) The concentration of calcium was elevated after the stimulation of pancreozyrain. This was due largely to the contamination of the bile, particularly the cystic bile. 4) The change of calcium concentration was considerably similar to that of amylase concentration in the pancreatic juice, even in the duodenal aspirate, suggesting that pancreatic acinar cells might be the place of calcium secretion. However, it was unknown whether calcium was secreted strictly corresponding to pancreatic amylase. 5) After the stimulation of secretin, the concentration of calcium was significantly higher in patients with pancreatic calcification, gallstone and common bile duct stone than in the control subjects. (163) AN APPLICATION OF 7sSES E L E N O M E T H I O N I N E TO PANCREOZYMIN-SECRETION (PS) TEST N. Sawabu, S. Hirose, A. Takada, and J. Takeuchi

The First Department of Internal

Medicine, School of Medicine, Kanazawa University In order to evaluate the mode of secretion of radioactive methionine into pancreatic juice, total and TCA-precipitable radioactivity in pancreatic juice and bile were measured after i.v. injection of 7sSe-selenomethionine in 5 dogs stimulated by continuous infusion with secretin and pancreozymin. Total and TCA-precipitable radioactivity in pancreatic juice became constant 2 hours after the injection of the radioisotope. The ratio of TCA-precipitable to total gradually increased and reached a plateau (over 90%) 2 hours after the injection. The amount of radioactivity in pancreatic juice became 2 to 3 times higher than that of bile, and the excretion of TCA-precipitable radioactivity into pancreatic juice was 5 to 6 times higher than that into bile. From these results it seems reasonable to carry out PS test 2 hours after the injection of 7~Se-selenomethionine. Clinically PS test was performed 140 minutes after i.v. injection of 7~Se-selenomethionine (100 pc) in 30 subjects including 14 cases with pancreatic diseases. Conventional three parameters, protein content and 7~Se-radioactivity were measured in duodenal juice.,The serial excretion pattern of total and TCA precipitable radioactivity was similar to that of amylase output in control. Both excretions of total and TCA precipitalbe radioactivity were correlated significantly to amylase output. There was a significant correlation between total and TCA precipitable radioactivities. From the excretion pattern of both factors, subjects having abnormality in 3 conventional parameters could be well differentiated from the control, and subjects with abnormality of 2 parameters were almost separated from the control. But there was no difference between group with abnormality in one parameter and control. These results suggest that change in amylase could be evaluated by measuring radioactivity in duodenal aspirate. Amylase determination could be substituted by measurement

Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(H) of radioactivity because of superiority of it's convenience and stability. (164) S C I N T I G R A P H I C S T U D Y OF CHRONIC PANCREATITIS WITH S P E C I A L R E F E R E N C E S T O ITS FUNCTION AND ETIOLOGY Y. Kuniyasu, H. Kakehi, G. Uchiyama, N. Arimizu, K. Okuda, M. Ohto, T. Kuroda, H. Saishyo, and T. Tanabe

Dept. of Radiology, and Dept. of 1st Internal Medicine, Chiba University School of Medicine Scintigrams of chronic pancreatitis were analyzed with special reference to their functions and etiologies. Twenty four patients with chronic pancreatitis, clinically diagnosed by the biopsy, surgery, or X-ray(calcification) were selected for this study. Scintigrams were classified into 3 types according to their image appearances. Whole pancreas (type I), a part of pancreas (type II) and no pancreas (type I I I ) is delineated in each group of scintigram. Eighty three percent of all patients (type I and II) showed the images of pancreas in scintigrams and rest of them (type III) showed no delineation of pancreas. The correlation of these scintigraphic patterns with the pancreozyminsecretin test was not proved. As the indicator of the pancreatic function, the 75Se-selenomethionine uptake of pancreas relative to that of liver (P/L ratio) was calculated from the scintigram especially m a d e for that purpose. The P/L ratio in a control group falls in 20-31% (average 25.7%), and chronic pancreatitis in 6-13% (average 8.6~ The chronic pancreatitis could be differentiated from the normal functioning pancreas by the P/L ratio, even in case the pancreas scintigram appeared normal. Th.e carcinoma of the pancreas showed low P/L ratio as in the chronic pancreatitis, so that the differentiation of these two was not possible. While the alcoholic pancreatitis includes all types of scintigraphic patterns (type I - I I I ) , chronic pancreatitis followed by the cholelithiasis showed type I scintigram.

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Two cases, the scintigraphic pattern changed from type I and II to type I I I within few years were demonstrated. (165) E F F E C T O F S E C R E T I N ON SELECTIVE PANCREATIC ANGIOGRAPHY (SELECTIVE GASTRODUODENAL ANGIOGRAPHY) T. Takashima and M. Shin

Department of Radiology, School of Medicine Kanazawa University Selective gastroduodenal angiography was performed in patients. In a group of control studies, several parameters such as vessel diameter, visualization of pancreatic vascular bed and pancreatogram are tabulated. Similar data are presented following the intra-arterial injection of secretin and comparison is made with control studies. Although the conventional serial arteriography constantly has not been successful in demonstrating the evidence of increase in uptake of contrast material in the pancreas following hormone stimulation, the X 2 direct serial magnification study demonstrate the secretin effect more obviously. (166) S T U D I E S O N C Y T O L O G I C EXAMINATION OF BILE FOR CARCINOMA OF PANCREAS M. Akashi, T. Moriyama, M. Uchimura, and R. Tsuchiya

Second Department of Surgery, Nagasaki University School of Medicine The value of the cytologic examination of bile for carcinoma of pancreas was investigated with an analysis of data thus obtained in 19 carcinomas of pancreas. For cellular materials of the cytologic examination of bile, not only bile but also physiologic saline and contrast medium, with which the biliary tract were washed, were used as well. These cellular materials were collected during the percutaneous transhepatic cholangiography, the laparotomy, the external biliary drainage and the autopsy.

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Malignant cells were identified cytologically in 11 of 13 carcinomas of the head of pancreas, an accuracy of 84 per cent and in one of nine carcinomas of the body and the tail of pancreas, an accuracy of 13 per cent. For studies on origin of cancer cells in bile, the postmortem materials of I 1 carcinomas of the pancreas were demonstrated. Data on the histologic sections suggested that cancer cells in bile might possibly originate from not only the invasive lesions of the biliary tract, but pancreatic juice with cancer ceils, which was mixed with bile in the obstructive biliary tract. In summary, the cytologic diagnosis of bile can be reliable for the definitive diagnosis of carcinoma of the head of pancreas, hut not helpful in establishing the diagnosis of carcinoma of the body and the tail of pancreas. (167) P A R O T I D S A L I V A AS A MEDIUM FOR THE DIAGNOSIS OF THE PANCREATIC DISEASES G. Kakizaki, N. Noto, T. Oizumi, T. Soeno, and T. Maeta.

Department of Surgery, Akita University School of Medicine T. Saito

Department of Surgery, Tohoku University School of Medicine Nine patients with pancreatic diseases and thirteen patients without pancreatic diseases were subjected for the investigation of parotid saliva. In these patients, pilocarpine was injected intramuscuarly with a dose of 0.13 mg per K g of body weight. After the beginning of salivary secretion, parotid saliva was collected for twenty-five minutes in every five minutes intervals. The results revealed that the volume flow of parotid saliva was reduced and the maximum bicarbonate concentration and amylase contents in parotid saliva were decreased in patients with pancreatic diseases.

A possibility was emphasized that changes of the m a x i m u m bicarbonate concentration and amylase content in parotid saliva might reflect the existency of the pancreatic diseases. (168) T H E E X A M I N A T I O N F O R A NEW METHOD OF AMYLASE ASSAY BY M E A N S O F B L U E S T A R C H S. Naito, T. Saito, K. Shimizu, T. Nakajima, M. Tanaka, T. Kin, and S. Sugiyama

Juntendo University Medical School Izunagaoka Hospital, Internal Medicine Blue Starch was designed by Aceska et al. of Swedish chemist to assay .the a-amylase in human serum, urine and duodenal juice (pancreatic juice). The dye Cibachron F 3GA conjugated at 6th position of glucose in maltose unit with insoluble situation to water and formed up tablets of each 200mg, whereby a-amylase hydralized the starch to maltose the dye solved in water and through 620rap colorimetric assay was available. This study was carried out to investigate the efficency of the Blue Starch method for an assay to amylase activity in serum, urine and duodenal juice. The Blue Starch method was assumed as a distinguished reproducibility with convenient technic and t h e relationship of this new method w i t h former designed methods such as Smith Roe or Caraway method was satisfactorily an outline. However, the low value within normal area of amylase activity was scattered and the best efficiency was observed from 300 to 10,000 unit. A practical problem was indicated that the protein contents in a sample influenced in assay, the activity of amylase in urine increased in order to add the bovin serum albumin previous incubation, as well as in the pancreatic juice by pancreozymin-secretin stimulation.

Proceedings of the 58th Annual Meeting, 1972--Tokyo--(II) (169) STUDIES ON DIAGNOSES OF PANCREATIC AND HEPATIC DISEASES BY T H E UNIVERSAL CAELOMOSCOPE H. Takayama, T. Tomono, N. Kamijo, Y. Kimura, T. Matsuo, M. Shimada, and B. Terashima

Suwa Red Cross Hospital M. Oda, S. Furuta, and K. Kashiwabara

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(170) STUDY OF PANCREATIC ENZYME SECRETION (II) THE MECHANISM OF A C T I V A T I O N AND DEGRADATION OF PANCREATIC J U I C E TRYPSINOGEN IN D U O D E N U M AND EFFECT OF BILE ON I T Y. Ishihara, A. Kuroda, N. Sato, T. Noro, H. Ishikawa, and Y. Tajima

Internal Medicine, School of Medicine, Shinshu University

1st Department of Surgery, University

S. Oka

In pancreatic juice some enzymes such as amylase (Am) and lipase are active, but the others such as trypsinogen (Tg), Chymotrypsinogen and procarboxypeptidase are inactive and activated by enterokinase (EK) in duodenal juice after secreted into duodenum.

Tokyo Welfare Pension Hospital M. Sugiura, M. Karasawa, and K. Ito

Sugiura Laboratory K. Takei

Takei Medical Optical Works The authors have made the universal caelomoscope which can be applied clinically for the diagnose of pancreatic diseases. By using of the caelomoscope and the gastrothermometer, the surfase temperature of liver and pancreas can be estimated precisely to the extent of 1/100~ We use Machida RX500 lightning model with cooling and heat proof attachment as the source of the light. The thermister was introduced into peritoneal cavity through this caelomoscope, and make its tip touched to a certain portion of hepatic surface or other aimed organ's surface. Patients submitted to this study are as follows; one case of chronic hepatitis, 1 cholangiolitic hepatitis, 1 cancer of gallbladder and 1 gastric ulcer. Lower temperature was noted on the surface of liver cysts than on the other part. In the case of carcinoma of gallbladder, the difference of temperature seemed to be more variable and wide. On visible surface of normal pancreas, it is higher 8/100~ in central than in peripheral region.

of Tokyo

Changes of Am. and Tg. and trypsin (Tr) in rabbit pancreatic juice and human duodenal aspirates were studied. In rabbit pancreatic juice total protein (TP), Am. and Tg. concentration changed in parallel manner and Am/TP, Tg/TP, Am/Tg ratio maintained almost constant level after tetragastrin, pancreozymin and acetylcholine stimulations. In human duodenal aspirates, however, Tr. and Am. changed independently and Tr/Am ratio increased according to the degree of bile content, which suggested accelerating effect of bile on activation of Tg. In the mixture of rabbit pancreatic juice, duodenal juice and bile, under incubation at 37~ Tg. was activated to Tr. but at the same time Tg. was rapidly degraded to inter protein and peptides, and addition of biles inhibited the degradation of Tg. and consequently increased activation of Tg. By in vitro experiments using pancreatic juice, Tg., Tr., Chymotrypsin (Chy) and EK, it is found that degradation of Tg. was made by Chy. and addition of calcium inhibited this process. In conclusion, pancreatic juice maintains constant Tg/Am ratio. Activation of Tg. to Rr. by EK in duodenum occurs concomi-

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tantly with degradation of Tg. which is caused by Chy. and inhibited by calcium and bile. (171) A C L I N I C A L S T U D Y O F PHOSPHOLIPASE A ACTIVITY I N P A N C R E A T I T I S (II) S. Hashihira, T. Nishii R. Mori, Y. Takeda, T. Yamadori, A. Wakabayashi, and S. Iwata

2nd Dept. of Internal Medicine Osaka Medical College A comparative study was conducted on phospholipase A (PLA) and amylase in pancreatitis and the relationship of PLA to red cells was discussed. The following observations were made. 1) Examination of the exocrine secretory function of the pancreas with the PS test revealed a significant positive correlation between PLA and amylase in non-calcified chronic pancreatitis, pancreatic calculus and the control. The secretory patterns also showed a similar trend. 2) In chronic pancreatitis, however, a dissociation of 32% was found between the two enzymes and compared to PLA, amylase was more strongly disturbed. 3) In acute pancreatitis, chronic pancreatitis and biliary diseases, PLA showed an abnormally high serum level compared to amylase and PLA was more closely related to abdominal pain than amylase. 4) Hemolysis occurred when human blood and PLA were mixed and incubated, but this phenomenon was inhibited by CDP-choline. (172)

ON THE CORRELATION OF CHRONIC PANCREATITIS WITH ACUTE PANCREATITIS AND CHOLELITHIASIS M. Shiraso, K. Tokutake, H. Sato, S. Matsuno, N. Haga, Y. Saito, Y. Suda, and T. Sato

The First Department of Surgery, Tohoku University School of Medicine, Sendal In the follow-up study of the complaints and

the pancreatic exocrine function in the patients who had been confirmed by surgery as acute pancreatitis, the diagnosis of chronic pancreatitis was obtained in 20.7% out of 346 patients. Secretin test was positive in 30 out of 101 patients of cholelithiasis. And pancreatic fibrosis was detected in 8 of 125 from w h o m pancreas biopsies were taken. T h e n chronic pancreatitis was confirmed in 3.8% of cholelithiasis in w h o m both exocrine function and histology were examined. It was also confirmed that the location of the gallstone was not correlated with the function and the histology of the pancreas. But The occurrence of chronic pancreatitis in the patients with cholesterol stone was twice as much as in ones with bilirubin stone. From these results, it was suggested that the chronic pancreatitis would be caused by the common etiologic background in which the cholesterol stone was formed, rather than by the mechanical factor of stones at the ampullar portion.

(173) A L C H O L I C C H R O N I C P A N C R E A T I T I S IN C H I B A T. K u r o d a and T. Tsunoda

Funabashi Central Hospital In our series of 32 chronic pancreatitis patients, 18 patients were associated with alcholism (56%), and 6 with gall-stones. Among young patients, a first pain attack appeared after 7 years of alcholism (about 70 gr. of ethanol per day), but among senior after 1 5 ~ 2 5 years (120~240 gr. of ethanol per day). A diabetic type curve for 50 gr. G T T . was present in 10 patients (56%), a border type curve in 3 patients, and a normal type curve in 5 patients. Liver fibrosis was present in 2 patients and non-specific reactive hepatitis in 5 patients with liver biopsy.

Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(II) (174) E X T E R N A L P A N C R E A T I C SECRETION AFTER OPERATION OF UPPER ABDOMEN T. K a m a t a , H. K a n n o , Y. Aneha, a n d K. Kikuchi

Dept. of Surgery, Sendai National Hospital This study was designed to detect the correlation between postoperative a b d o m i n a l p a i n a n d external pancreatic secretion after operation of u p p e r a b d o m e n . Pancreozymin-Secretin test was performed a few days after operation by the use of ameliorated Dreiling-type tube indwelt in d u o d e n u m d u r i n g operation. Additionally d e t e r m i n a t i o n of amylase activity in serum a n d urine, blood sugar a n d biopsy of pancreas were carried out. These examinations were done in 62 cases comprising 25 cases of gastric cancer, 20 of gastric or d u o d e n a l ulcer, 15 of gall stone a n d two of cholecystitis. Those cases were classified into three groups by the grade of d a m a g e of p a n c r e a s d u r i n g operation: viz. R I with no d a m a g e such as by cholecystectomy, R 2 with d a m a g e such as by operation of gastric cancer or of p e n e t r a t i n g gastric ulcer, R 3 with severe d a m a g e by extended radical gastrectomy for gastric cancer. Results obtained were as follows. 1) M a x i m u m b i c a r b o n a t e concentration was found in 34% of R , cases, 54 ~/O of Ro a n d 8 2 % of R 3 cases. 2) Decrease of amylase o u t p u t was found in all the cases of R3, a n d of R 2 with exception of merely one case. 3) Postoperative a b d o m i n a l pain was complained by eleven cases, seven of 24 R~ a n d R a cases (29(}/o) a n d four 38 R 1 cases

(10%). 4) A m o n g twelve cases undergoing p a n c reatic biopsy, only two were a b n o r m a l , showing slight fibrosis, one of which was a b n o r m a l also by pancri~ozymin-secretin test while a n o t h e r one was normal. 5) T h e r e was no correlation between the result of pancreozymin-secretin test a n d

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amylase activity of urine or serum. (175) R E - E X A M I N A T I O N O F THE PEPTIC ULCERATION IN PANCREATITIS M. Abe

Hiratsuka City Municipal Hospital K. I m a m u r a , O. K o n d o , Y. Yuki, a n d S. O m a t a

Yokohama City Municipal Hospital T h e purpose of this p a p e r is to re-examine t h e peptic ulceration in pancreatitis. T h e association between peptic ulceration a n d pancreatitis has been examined in a series of 234 patients with pancreatitis, 11 of w h o m h a d painless pancreatitis disease. Radiological evidence of peptic ulceration a n d gastrointestinal h a e m o r r h a g e was found in 43 (18.4%) of these w h o h a d h a d attacks of pancreatitis, b u t the incidence of peptic ulceration was in fact only 9.4o/0 . Chronic pancreatitis was diagnosed by means of surgery, the presence of pancreatic calcification on radiographs of the a b d o m e n , or by the finding of a n a b n o r m a l i t y in the pancreozymin-secretin pancreatic exocrine function test. Chronic pancreatitis was also diagnosed in patients with a strongly suggestive story of pancreatitis in w h o m two or more of the following biochemical a n d radiological a b n o r malities were present: a borderline pancreatic function test, a n elevated urine a n d serum amylase level, a positive provocative enzyme test, or a n a b n o r m a l glucose tolerance test a n d hypotonic d u o d e n o g r a p h y . T h e fasting serum gastrin level of patients with chronic pancreatitis was significantly low c o m p a r e d to those in n o r m a l controles. T h e present observation would suggest t h a t in m a n y cases of these it can not be a t t r i b u t e d to peptic ulceration except gastrointestinal h a e m o r r h a g e as to serum gastrin level.

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(176) T H E S T U D Y O N O R G A N RELATIONSHIP BETWEEN BILIARY T R A C T A N D S T O M A C H (I) : O N THE FUNCTION OF GALL BLADDER AFTER GASTRECTOMY AND POST GASTRECTOMY CHOLECYSTITIS : S. O k a m o t o , H. N a g a h a r a , H. M o t o y a m a , H. W a t a n a b e , T. Maekawa, T. M i y a k a w a , Y. W a t a n a b e , Y. A n a z a w a , a n d T. M u r a k a m i ,

Department of Surgery, Juntendo Univdersity, School of Medicine In recent years, with the progress of gastric surgery, the cases of total gastrectomy a n d fundectomy are increased. But the same time, more considerations have to be p a i d for the organ relationship between biliary t r a c t a n d stomach, as the vagus nerves are cut during the surgery. This is to report t h e clinical study a n d the function of g a l l b l a d d e r after gastrectomy. I. C L I N I C A L S T U D Y A m o n g the 2351 cases of gastric surgery for the past ten years, 65 cases, 2.6% of cholelithiasis were found. Post gastrectomy cholecystitis with stone were seen in seven cases; Most of cases were a c c o m p a n i e d with r e m a r k a b l e i n f l a m m a t i o n of gallbladder, c o m m o n duct stones a n d intrahepatic stone. Four cases were complicated with acute gangrenous cholecystitis in early period after gastrectomy. These cases showed r e m a r k a b l e inflammation a n d no stones. T w o cases were seen after total gastrectomy a n d other two cases were after Billroth I I method. II. GALLBLADDER FUNCTION BEFORE AND AFTER GASTRIC SURGERY. Both the bile flow curve at the level of gallbladder a n d cholecystography are t a k e n at the same time after the venous injection of 131 IBSP 10/to pre a n d post operatively to the 33 cases of the stomach diseases a n d to 11 cases as control. T h e bile flow curve of gall b l a d d e r was shown as % / m i n by the semi-logalithm diagram a n d by o b t a i n i n g the ratio of bile flow from the gallbladder, gallbladder function

was studied. C o n t r a c t i o n activity of gallbladder is generally decreased by the gastric surgery, t h a t is more r e m a r k a b l e in cases with t r u n cal vagotomy c o m p a r e d with control cases. T h e cholecystographies pre a n d post truncal v a g o t o m y in dog a n d the decrease of weight of h u m a n gall stone p u t into t h e canine gallbladder were also stqdied. T h e r e are m a n y papers on g a l l b l a d d e r function after gastrectomy but our study revealed t h a t g a l l b l a d d e r is dilated a n d its function is decreased by the gastric surgery, particularly by t r u n c a l vagotomy. This is supposed to be by cutting the vagus nerve. (177) G A L L S T O N E F O R M A T I O N AFTER GASTRIC RESECTION T. M o t o y a m a , T. K a w a m u r a , a n d Y. K u s a k a

Department of Surgery, Iwate Medical College, Morioka T h e present c o m m u n i c a t i o n is to report nine cases of bile duct diseases developed after gastric resection. Seven out of nine cases h a d gallstones a n d a n analysis was m a d e concerning the m e c h a n i s m of gallstone formation in connection with bile stasis,. postvagotomy dyskinesia a n d bile infection. Seven patients originally u n d e r w e n t either Billroth I or I I operation for gastric ulcer in five a n d d u o d e n a l ulcer in two cases. D u r a tion after gastric resection a n d the developm e n t of gallstones r a n g e d from five to 28 years with the average of 14 years. Five out of seven patients h a d an initial s y m p t o m of tight h y p o c h o n d r a l g i a a n d fever was associated in t h r e e patients. U p o n laparotomy, t h e g a l l b l a d d e r was generally distended a n d mixed stones with p r e d o m i n a n t bilirubin c o m p o n e n t were found in most of the cases. Pancreozymin-secretin test after gastric resection revealed disturbed p a n c r e a t i c exocrine secretion w h i c h ~'nJicated i m p a i r e d contraction of t h e gallbladder. Cholecystogram taken one m o n t h after gastric resection showed distended ~.allbladder with poor con-

Proceedings of the 58th Annual Meeting, 1972--Tokyo--(H) tractility after ingestion of ,egg-yolk in 17 percent. Contamination of duodenal juice was found in 38 percent of hyperacidity and 50 percent of hypoacidity cases with higher incidence in cholelithiasis than in gastric lesions. After operation, the rate of contamination increased up to 63 percent in cholecystectomy cases and 100 percent in gastrectomy cases and the findings were the same even after three months.

(178) F O L L O W - U P S T U D I E S O F BILIARY TRACT SURGERY M. Sugiura, F. Shima, S. Abe, S. Ichihara, M. Nomura, T. Ushiyama S. Futagawa, and M. Ishida

2nd Department to Surgery, Faculty of Medicine, Tokyo University The follow-up studies of 81.3% of 267 patients who were subjected to biliary surgery during 7 years were presented. The biliary stones, papilla The

common causes of the sequelae of tract surgery were residual or reformed stricture of biliary tract, stenosis of of Vater, and portal hypertension. operative procedures, such as stone

removal with sphincterplasty, hepaticojejunostomy, sphincterplasty alone, and esophageal transection with para-esophagogastric devascularization and splenectomy, were needed on 61 patients with postbiliary surgery syndrome. The incidence of the sequelae due to residual stones could be reduced by the radiological examinations and instrumental explorations during surgery. There were some cases who had dilatation of the common bile duct without stenosis of the papilla of Vater at first operation. Sphincterplasty could be often beneficial in such cases. The cholangiograms of some cases after first surgery revealed the dilatation of the common bile duct. Further studies should be done for the evaluation of sphincterplasty as a therapeutic procedure for these patients.

(179)

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A STUDY OF PERCUTA-

NEOUS BILIARY DRAINAGE G. O b a t a et al.

First Department of Surgery, Chiba University School of Medicine In cases of obstructive jaundice, drainage operations such as cholecystostomy have been usually performed before radical operation, because one stage operation often brings great hazard. But the drainage operation can not always be performed without any trouble. So, easier and safer method of drainage was studied. After percutaneous transhepatic cholangiography was carried out to visualize the position and the cause of the obstruction, a needle (external diameter 2 mm.) covered with a polyethylene tube is introduced percutaneously into the dilated intrahepatic bile duct and withdrawn leaving the tube in the punctured bile duct. Then through the tube, a polyvinyl tube is led into the common hepatic duct or choledochus for biliary drainage. The effect of the percutaneous drainage was similar to that of the drainage operation. This procedure was carried out in 40 patients. And after jaundice had been relieved, one stage operation performed in 23 cases. Percutaneous biliary drainag is a useful procedure that ensures one stage operation for obstructive jaundice and enables to examine the bile or to obtain cholangiograms repeatedly. It can be also utilized for lavage of the bile duct and infusion of agents (e.g. antibiotics for suppurative cholangitis or chelating agents for intrahepatic calculi) into the bile duct.

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Proceedingsof the 58th Atinual .Meeting, 1972-- Tolryo--(H)

(180) P H Y S I O L O G I C A L A N D PHOTO-OPTICAL OBSERVATION USING T-TUBE AFTER BILIARY SURGERY

J . Inoue, S. Miyaishi, T. Sasaki, Y. K u r o y a n a g i , T. Sato, H. Kato,

Y. Sugiyama, K. Suzuki, M. Abo, M. T a k e u c h i , E. T a n n , K. K i m u r a A. Iwaya, H. Takahashi, a n d K. O n o

T h e 80 gallbladders excised surgically were e x a m i n e d by X - r a y filled with radiopaque. T h e a b n o r m a l findings (shapes) of p h o t o graphics in relation to macroscopic a n d histologie findings were studied. T h e characteristic patterns of t h e m were as follows: 18 cases radiologically characterized by a symmetrical constriction of the gallbladder were simply due to n a r r o w i n g of the l u m e n except 1 case. E i g h t e e n cases d e m o n s t r a t i n g radiologically a n unilateral constriction were also noted. This was due to inflammatory scar or b e n d w i t h o u t scar. T h e differentiation of those two factors could be m a d e by irregularity of the m a r g i n of the constricted wall. Nine of the 10 cases with a n irregular m a r g i n h a d inflammatory scar, whereas 3 of the 8 cases without it were the bended gallbladder. T h e irregular serration of the gallbladder was observed in 48 of 63 cases excluding 17 cases of the constricted gallbladder. This finding was considered to be due to g r a n u l o m a t o u s i n f l a m m a t i o n of the muscle layer a n d papillary proliferation of the mucosa. I n the r e m a i n i n g 15 the regular contour of the gallbladder was demonstrated. It was to be noted, however, a correlation between the severity of the irregular serration a n d t h e thickness of the gallbladder was not always parallel. I n 28 of 80 cases the radiological diverticulum-like out pouchings (herniations) of the gallbladder were demonstrated radiologically. These were confirmed histologically similar to Aschoff-Rokitansky sinuses. Fourteen of t h e 28 cases were associated with a constriction of the gallbladder.

Department of Surgery, Faculty of Medicine, Hirosaki University, Hirosaki (Director: Prof. K. Oh-Uti) T h e purpose of this study is to know the physiology of bile flow in the patients with gallstone disease who have u n d e r g o n e biliary operation in our clinic. T h r e e experiments were simultaneously performed for this study, such as radiocinem a t o g r a p h y with c o n c o m i t a n t electromyog r a p h y of O d d ' s muscle, m a n o m e t r i c measurem e n t of bile d u c t a n d the p a i n p r o d u c i n g test by raising t h e biliary pressure via the tube. T h e results o b t a i n e d are as follows: 1) Bile flow to the d u o d e n u m was controled by O d d i ' s muscle independently of d u o d e n a l wall muscle. 2) T h e t e r m i n a l portion of c o m m o n bile duct a p p e a r e d to have not only contractive m o v e m e n t b u t d y n a m i c action e v a c u a t i n g i n t r a d u c t a l contents into the d u o d e n u m . However, in the cases h a v i n g a long t e r m history of intracholedochal gallstones, t h e r e were showed neither the contractility n o r evacuating m o v e m e n t . 3) T h e basal pressure of the bile d u c t was f o u n d e d from 80 m m H 2 0 to 142 m m H 2 0 , a n d the 3 cases showing high level pressure revealed residual stones. 4) T h e p a i n - p r o d u c i n g pressure of the c o m m o n bile d u c t was showed from 850 m m H 2 0 to 210 m m H 2 0 . In the case i n d i c a t i n g m i n i m u m value of p a i n - p r o d u c i n g pressure residual stones were founded in the c o m m o n bile duct. (181) F U N D A M E N T A L S T U D I E S ON X-RAY DIAGNOSIS OF GALLBLADDER DISEASES

C. Kido, a n d K. H i b i n o

Aichi Cancer Center Hospital, Nagoya

Proceedingsof the 58th Annual Meeting, 1972-- Tokyo--( H )

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(182) T H E D I A G N O S I S O F C A N C E R OF THE PANCREAS AND BILIARY S Y S T E M BY C O M B I N E D P E R C U TANEOUS TRANSHEPATIC CHOLANGIOGRAPHY, HYPOTONIC DUODENOGRAPHY AND CYTOLOGIC METHOD

AI-P. continued to decrease during three weeks after the onset of jaundice, but remained higher than the normal level. It should be notewothy that the enzyme activities decreased in spite of the persistent obstructive jaundice with cancer.

M. Kishikawa, T. Takeuchi, H. Murate, A. Tanabe, M. Kozuka, M. Ito, N. Kato, Y. Yazaki, K. Goto, M. Miyaji, K. Suzuki, K. Ito, and J. Yokoi.

(183) P A N C R E O Z Y M I N CHOLECYSTOGRAPHY

1st Int. Med. Nagoya City Univ. Percutaneous transhepatic cholangiography (P.T.C.) and hypotonie duodenography (H.D.G.) were taken at same time for diagnosis of the pancreas and biliary system. Furthermore, cytologic diagnosis of the intrahepatic bile and duodenal juice which obtained during these procedures, was combined to approach more reliable diagnosis. For cytology, modified cytologic technic was employed in this study, i.e. the sample was suspended in chilled saline water for protection of cellular degeneration and centrifused and smeared with "Autosmear" for collection of the ceils. O f 95 patients, 43 cases were cofirmed to be cancer and 52 cases to be benign lesion in the pancreas and biliary tract by operation or autopsy. O f 34 cases with cancer examined cytologically, 22 cases were positive in the bile or duodenal juice. All of 52 patients without cancer were negative and no false positive. Malignant cells were detected in high percentage in carcinoma of the bile duct and gallbladder in the bile, and so did in carcinoma of Vater's ampulla in the duodenal juice. Five patients with cancer were difficult to differentiate from benign lesion by the combined X-ray examination of P.T.C. and H.D.G., but three were positive by cytology. Therefore, the accuracy of diagnosis of cancer in the pancreas and biliary system was improved by the combined application of the three diagnostic methods. In ten of seventeen cases with cancer, elevated activities of G,O.T., G.P.T. and

I. Endo*, S. Kato*, M. Miyazaki*, N. Murayama*, and A. Kawamura**,

*Department of Surgery, **Department of Internal Medicine, Tokyo Dental College Serial cholecystography using pancreozymin (Pz) 2 u / K g as a gallbladder stimulant was performed and changes in gallbladder, biliary tract and duodenum, complains of the patients were observed in 9 controls and 20 patients who complained of right upper quadrant abdominal pain - 9 cystic duct syndrome (C.D.S.), 4 adenomyomatosis of the gallbladder, 2 acute cholecystitis, 2 cholelithiasis, 3 cholecystopathy. In the control subjects, the extent of gallbadder shadow became minimum at 10 min after Pz injection and Ca 40% on the average compaired with before Pz injection. At 5 min the extent was more than 75% in most of the patients, but in most of the controls less than 75%. In C.D.S. patients, the reduction of the extent was diminished and prolonged, in 5 cases even a temporary increase of the extent was noticed, the extent of shadow was more than 75~; at 5 min in 7 C.D.S. patients, and was minimum in 15 or 30 min. Three patients complained mild right upper quadrant abdominal pain. Duodenum was visualized well at 3 to 10 min and disappeared at 15 min in the controls, but in serious C.D.S. patients, it was visualized late at 15 or 20 min or non-visualized therefore the impaired visualization of duod e n u m may be one of the indicator for impaired gallbladder evacuation. In 3 adenomyornatosis patients whose cholecystogram showed remarkable stricture

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Proceedings of the 58th Annual Meeting, 1972-- Tokyo-- (H)

which were confirmed at operation in the mid-portion of the gall-bladder, infundibular portion became promptly small so far as 33 to 12% at 3 or 5 rain after the injection of Pz, then dilated promptly to 74 to 60% at I0 or 15 min, whereas fundal portion showed remarkable impaired contraction and the extent of the shadow was about 90% at 5 rain. The reduction of the shadow of fundal portion in 2 cases progressed over 30 rain. These findings may be available for the differential diagnosis between mere bend and stricture caused by adenomyomatosis. (184) P E R C U T A N E O U S C H O L A N GIOGRAM, HYPOTONIC DUOD E N O G R A M AND D U O D E N O F I B E R S C O P I C F E A T U R E IN T H E I N F L A M M A T O R Y DISEASES O F PAPILLA

1st Dept. of Int. Med., Chiba Univ. School of Med. The features of inflammatory diseases of papilla are followed. (1) The choledochusend in the percutaneous cholangiogram is described as the stenosis I) 2) 3) 4) 5) 6)

7) 8)

Symptoms i) Upper abd. pain (colic) 2) Fever (38~ Rt. Hypochondralgia (colic) 1) Upper abd. pain (colic) 2) Jaundice 3) Fever (41~ Heavy feeling on the back (Rt.) Rt. hypochondralgia (colic) 1) Rt. hypochondralgia (colic) 2) Transient jaundice 1) Rt. hypochondralgia (colic) 2) Nausea and vomiting Rt. hypochondralgia (colic)

(3) (4)

(5)

or sclerosis in constant. The papillary shadows in the hypotonic duodenogram are variable in shape and aize. The endoscopic papillary features are variable too. The histological changes in papilla are discrepant between the biliary side and the duodenum. The diseases of papilla in biliary side is of consequence than in duodenum.

Conclusion Percutaneous cholangiography is useful for diagnosis of the papillary diseases, but hypotonic duodenography and duodenofiber scopic findings are little. (185) F I N D I N G S O F P E R C U T A NEOUS TRANSHEPATIC CHOLANGIOGRAPHY OF THE POSTCHOLEC Y S T E C T O M Y CASES W I T H C O M PLAINTS B. Murohisa Gastroenterological Department, Hamamatsu Medical Center. Percutaneous transhepatic cholangiography was carried out on fifty cases, in which 8 cases were post-cholecystectomy cases for the past one year. Analysis of the findings of post-cholecystectomy cases are shown in the table.

T. Ono Int. Med., National Cancer Center Hospital. M. Ohto, et al.

No.

(2)

PTC Findings

DIC Not done Well visualized Not visualized Faintly visualized Faintly visualized

1) Dilatation of common duct. 2) A stone in common duct. Two stones in common duct. 1) Dilatation of common duct. 2) A common duct stone. Cystic duct remnant. Stricture of sphincter of Oddi.

Dilatation of intrahepatic duct. Narrowing of common duct. Shortening of common duct. Cystic duct remnant. Choledochal cysts (intrahepatic and common duct.) Not visualized 2) Narrowing of common duct. Poor Ascaris in intrahepatic duct. Visualization Faintly visualized

1) 2) 3) 4) 1)

Proceedingsof the 58th Annual Meeting, 1972-- T&yo--( H ) (186) A C O M P A R A T I V E S T U D Y O F SURGICAL FINDINGS AND C H O L A N G I O G R A M S I N BILE D U C T CANCER, WITH SPECIAL REFERENCE TO PERCUTANEOUS DOUBLE CHOLANGIOGRAPHY M. U c h i m u r a S. Hirai, M. Akashi M. Furukawa G. Nakashima H. Furuse, and R. Tsuchiya

Second Department of Surgery Nagasaki University Percutaneous cholangiography is the best diagnostic procedure to find the organic change of the bile duct. It is difficult, however, to evaluate indication for surgical removal of the bile duct cancer on X-ray findings, because reliable details of obstructed region such as depth of cancerous infiltration and intraductal morphology are not available in the routine method owing to poor mixture of the bile and the contrast medium. Since May 1963 we have performed percutaneous perhepatic cholangiography on 279 cases, dividing the findings into five types: V-type, U-type, straighthorizontal type, rat-tailed type, and stenotic type. This time we evaluated routine cholangiography and the so-called "double cholangiography" technique in which air is injected after saline water irrigation of the bile duct, comparing with surgical findings on 28 cases of bile duct cancer operated since September 1969. Excluded from this study are bile duct cancer in the liver and gallbladdef cancer. In upper and middle bile duct cancer, there were two V-types, one U-type, four horizontal types, and two stenotic types of the upper bile duct and three stenotic types of the middle bile duct. In lower bile duct cancer, there were three stenotic U-types of the upper bile duct and two U-types of the middle bile duct. Ampulla cancer had two U-types of the upper bile duct and pancreatic head cancer had three such types. Resection of the lesions were possible in four middle bile duct cancer cases, and five lower bile duct cancer cases, and three am-

197

pulla cancer, 12 cases in total. They formed horizontal type in middle bile duct cancer and U-type in lower bile duct and ampulla cancer. However, U-type was also found in the inoperative cases of pancreatic head cancer causing difficulty in differentiation. Double cholangiography was performed on 22 of these 28 operated cases, showing V-type and stenotic type as demonstrated in routine cholangiography without elasticity of the wall. Horizontal type becomes U-type in double cholangiography and the wall is dilated easily. The final end of the bile duct is better visualized in lower bile duct cancer and ampulla cancer. U-type of pancreatic head cancer took the shape of V-type with stenosis of the lower bile duct. Resection of the lesion was possible in four of five middle bile duct cancer which presented four U-type of the middle portion of the bile duct, four U-types of the lower bile duct and three irregularity of the end portioon of the common bile duct demonstrating good wall elasticity. Thus U-type stenosis and irregular common bile duct end in double cholangiography are good indication for resection of cancerous lesions. (187) P A T H O L O G I C A L S T U D I E S ON THE PAPILLARY CANCER T. Fukuda, F. Hanyu, N. Sakakibara, H. Suzuki, H. Ide, and K. M o m m a

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical College Paying some regards to its histology, we classified papillary cancer into the following four groups; 1) papillary cancer on the duodenal side, 2) so-called papillary cancer, 3) cancer in the lower end of the common bile duct, 4) cancer in the distal end of the pancreatic duct. So-called papillary cancer was found in 5 cases, the cancer in the lower end of the common bile duct in 5 cases, the papillary cancer on the duodenal side in 3 cases and

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Proceedingsof the 58th Annual Meeting, 1972-- Tokyo--(H)

the distal end of the pancreatic duct in 1 case. The last one (cancer in the distal end of the pancreatic duct) was identified histologically. Radical resection was performed in 12 cases, among which the smallest one is socalled papillary cancer and the largest one is cancer arised from the lower end of the common bile duct. All the cases of the papillary cancer on the duodenal side and the so-called papillary cancer were polypoid type and 2 out of 5 cases of the lower end of the common bile duct were ulcerated type.

sulfate

(1.5%)

and

minute

quantities

of

xylose and arabinose. Contents of threonine, serine and proline were relatively high in the protein moiety. The data indicated that Fr. 3W was a sulfated glycoprotein. Since Fr. 3W was suggested to be an abnormal component in the bile, an important role of sulfated glycoprotein (s) in gallstone formation was indicated. (189) S U R F A C E - C H E M I C A L STUDIES ON THE SIGNIFICANCE OF LITHOCHOLIC ACID ON G A L L S T O N E F O R M A T I O N (I) M. H a g a n o and T. Furusawa

(188) A S U L F A T E D G L Y C O P R O T E I N , CAPABLE O F C O A G U L A T I N G CALCIUM CARBONATE, ISOLATED FROM PATHOLOGICAL HUMAN BILE H. Nagashima, T. Matsushiro, N. Suzuki, T. Saitoh, N. Nakamura, W. Takahashi, T. Maeta, T. Hatanaka, N. Kobayashi, and T. Sato

The First Department of Surgery, Tohoku University School of Medicine Water-soluble fraction (Fr. 1) obtained either from pathological human bile or normal human bile was fractionated centrifugally in the presence of salts to give six fractions (Frs. 2, 2R, 3,4,5, and 6). O f these fractions, the major fraction (Fr. 3) obtained from the pathological bile was shown to have strong coagulation effect for calcium carbonate suspension in water, whereas any coagulation effect was not found in the fractions obtained from the normal bile. Gel-filtration on DEAE-Sephadex A-25 of Fr. 3 from the pathological bile afforded Fr. 3W. This fraction had the similar coagulation effect for calcium carbonate suspension to Fr. 3. Fr. 3W showed a single band each at p H 3.0, p H 7.0 and p H 9.0 in cellulose acetate electrophoresis. This fraction contained galactose (27.2%), glucosamine (17.3%), galactosamine (9.6%), L-fucose (15.9%),

1st Dept. of Surg., Fac. of Med. Kyushu Univ. It has been well established that bile salts and phospholipids chiefly lecithin play the main roles in the solubilization of cholesterol in bile. The existence of lithocholic acid was disclosed by recent GLC studies. The aim of the present study has been to clarify the effect of lithocholic acid on the solubilization of cholesterol by bile salts and lecithin. All experiments were carried out at 23•176 First, the solubilization of sodium lithocholate by bile salts (sodium cholate and sodium deoxycholate), lecithin systems was studied by turbidimetry. The amount of solubilized sodium lithocholate by bile salts was 7.8%, and that by bile salts lecithin 6.1%. The time dependency of solubilization of cholesterol was thoroughly checked. The amount of solubilized cholesterol decreased with increasing amount of sodium lithocholate to some extent. The solubilization of cholesterol by bile salts, lecithin was dependent on the L/B ratio, below 0.25 the co-existence of sodium lithocholate decreasing the amount of solubilized cholesterol, but above that hardly altering it in tt'_e checked concentration range.

Proceedingsof the 58th Annual Meeting, 1972-- Tokyo--( H) (190) R E L A T I O N S H I P B E T W E E N BILE C O M P O S I T I O N A N D G A L L STONE FORMATION IN SQUIRREL MONKEYS T. Osuga and O.W. Portman

Department of Primate Nutrition, Oregon Regional Primate Research Center, Beaverton, Oregon 97000, and the Department of Biochemistry, University of Oregon Medical School, Portland, Oregon, U.S.A. We investigated the mechanisms of cholesterol gallstone formation in squirrel monkeys by measuring cholesterol, phospholipid, and different bile acid concentrations in gallbladder and hepatic bile and in the gastrointestinal tract. A group of monkeys which was fed a semipurified diet that resulted in a high incidence of gallstones (Group 3) had higher concentrations of cholesterol relative to phospholipid and bile acids than monkeys fed a corresponding diet with an unsaturated fat and no cholesterol Group 2). Monkeys fed a commercial natural diet (Group 1) had no gallstones and the lowest concentration of cholesterol relative to the cholesterol-stabilizing factors in the gallbladder bile. T h e animals in Group 2 with gallstones had higher relative cholesterol concentrations than monkeys in that group without stones. The presence of gallstones in individuals was predicted from gallbladder bile compositions and any one of several indices of the m a x i m u m level of cholesterol that could be stabilized in micellar forms. In most monkeys the concentration of cholesterol relative to bile acids and phospholipids was higher in hepatic than in gallbladder bile, although the proportions of different bile acids were similar in the two types of bile. Deoxycholic acid was present in relatively low concentrations in the biles of animals from Group l, although deoxycholic and lithocholic acids, which are bacterial products, were produced in the large intestine of all animals. T h e poor size of taurocholic acid was much higher in monkeys from Group 1 than in the other monkeys.

199

(191) A S C A N N I N G E L E C T R O N MICROSCOPIC STUDY OF HUMAN GALLSTONES T. Ogata, S. Tanaka, K. Takahashi, and H. Kibayashi

Dept. of Surgery, Okayama University Medical School, Okayama The fine surface and cut-surface structure of gallstones were observed under a scanning electron microscope. In cholesterol gallstones, the fracture surface generally showed a crystalline plane radiating pattern, often with dendritic growths around the nucleus. O n the surface or fractured plane of a cholesterol stone, parallelogram crystals or corrugated crystals were sometimes seen. In higher magnification, the surface of a crystalline plane is seen to be composed of lamellae of about 200 A in thickness, which was frequently associated with spiral growth. In bilirubin stones, an accumulation of spherical granules 2 or 3 microns in diameter, or mud-like amorphous substances were observed. In the laminated stones, layers with different structures 30 microns in thickness were arranged alternately. From infrared spectroscopic analysis, it was elucidated that the layers with amorphous structure were composed of bilirubin, the layer of multiple holes were bilirubin and lipid, and the columnar crystals were cholesterol. Lipid stones were composed of plane-like or leaf-like crystals. Limy biles were composed of calcium carbonate or calcium oxalate. In the limy bile with calcium oxalate, needlelike crystals 30 microns in length were assembled in an arrangement which tended to give the whole a spherical structure. In the limy bile with calcium oxalate and calcium carbonate, cuboid crystals, and spherical or oval crystals were also observed in addition to needle-like crystals.

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Proceedingsof the 58th Annual Meeting, 1972-- Tokyo--(H)

(192) S T U D Y O F E T I O L O G I C A L DISPOSITION OF ACUTE PANCREATITIS WITH CHOLESTEROL STONE H. Yamazaki, K. Komaki, H. Tanimura, and Y. Hikasa

Dept. of Surgery R. Ogawa

Dept. of Intern. Med. Kyoto University The difference in endemic incidence of acute pancreatitis with cholesterol stones is considered probably due to different dietary customs, such as Japanese or European. We had previously noticed that metabolic disturbance in the essential fatty acids (EFA) has a close relationship to the formation of cholesterol stones. In the same way, the high incidence of gallstones in patients with acute pancreatitis could also he explained by disturbed metabolism of EFA as a result of the following examinations. 1) Trypsin or autogenous bile decreased permeability of the membranes of pancreatic acinar cells in hamsters fed on lithogenic (EFA dificient) diets, respectively. Addition of bile on trypsin more decreased it due to stimulated endogenous trypsin. 2) Urinary pancreatongenic isoamylase in lithogenic diet groups showed higher level than those in hamsters fed on non-lithogenic diets. 3) In h u m a n cholecystectomized cases, patients with cholesterol stones showed that urinary pancreatogenic isoamylase maintained high level not only before operation but also 2 or 4 months p.o. later except transient increase due to surgical injury. 4) In patients with pigmented stones or mixed stones it showed low level and rapidly recovered from a transient increase due to infection or operation. (193) A N E W O X I D A T I O N ENZYME PRESENT IN HUMAN SALIVA H. Nakagawa

Tokyo National Chest Hospital

Findings concerning the physiological role of saliva in the alimentary canal in man are not so many. This means that the salivary contents have not been estimated to be significant. T h e author found recently a new oxidation enzyme which catalyzes promptly the oxidation of Rifampicin, which is a semisynthetic antibiotic, in h u m a n saliva, and has been investigating its catalytic properties. The saliva obtained from normal subject was centrifugalized for 20 minutes at 10,000 r.p.m at 5~ and its supernatant solution was used. When Rifampicin was incubated with the centrifugalized saliva in acid condition corresponding to the physiological acidity of gastric juice, it was observed that Rifampicin was promptly and remarkably oxidized into Rifampicin-quinone. The oxidation velocity was rapid being completed within 15 minutes at room temperature, and the rapid oxidation with the salivary catalyst was a striking contrast to a slow autooxidation of Rifampicin in the presence of divalent copper. At room temperature around 20~ the oxidation catalyst of saliva was unstable being destroyed nearly in a few hours. However, under the keeping at 5~ its activity was maintainable in relatively stable for several days. The original enzyme present in saliva having about neutral p H was substantially inactive, and its catalytic activity first appeared when the acidity of the saliva was brought to p H below 3. The activated enzyme also restored reversibly into the original one by varying the p H above 4. Such a p H depentent activity of this enzyme was very similar to the activation of pepsinogen into pepsin in a strong acid condition. The oxidation of Rifampicin by the salivary enzyme was completely inhibited in the presence of cyanides, cysteine, H2S , and further inhibited partially with D E T A , and any thio-compounds. This suggests that the present enzyme with copper

which

may

be

an

oxidase

seems to be essential

for its activity. The hydrogen acceptor participating in the enzymatic oxidation

Proceedingsof the 58th AnnualMeeting, 1972--Tokyo--(II) of Rifampicin was decided to he molecular oxygen, from an evidence that the 0 2 uptake accompanied by the Rifampicin oxidation with the enzyme fractions which had been isolated from saliva was correlated well with its oxidation activity, on a gasmetric analysis in a Warburg's manometer. Physiological meaning about the presence of such an oxidase in saliva has not yet been clarified. However, it may be imagenated that this enzyme must have any physiological function in the alimentary canal, perhaps important as a preliminary treatment of certain substances prior to their intestinal absrption. It was further pointed out that there was a significant individual difference in the enzyme activity of saliva which was sampled in fasting. (194) C L I N I C A L A P P L I C A T I O N OF S I A L O S C I N T I G R A M AND R A D I O S I A L O G R A M W I T H 99mTC IN PATIENTS W I T H COLLAGEN DISEASES M. Osada

Department of Gastroenterology H. Koizumi

Department of Internal Medicine M. Katayama

Department of Radiology H. Sakamoto

Department of Otology Kawasaki City Hospital We presented before the 57th General Meeting, the Japanese Society of Gastroenterology, that the technical advances about Sialoscintigram and Radiosialogram, such as introduction of 99mTC and the new collimator, had further enforced its clinical utility. The subjects were 23 patients with collagen diseases (SLE: II, PSS:2,RA:3, RA with PSS: 2, Sj6gren's syndrom:I, D M : I) and the allied diseases (Wegener's granulomatosis : I, Beh~et~ syndrome: I, colitis ulcerosa: I). This radioisotopic method indicated the salivary dysfunction despite absence of xerostomia in the cases of collagn diseases and the allied diseases.

201

(195) M E A S U R E M E N T OF TRANSMUCOSAL POTENTIAL DIFFERENCE OF T H E H U M A N S T O M A C H UNDER ENDOSCOPIC CONTROL T. Manome, M. Sesoko, M. Kobayashi, Y. Komine, Y. Saito, N. Watanabe, Y. Okabe, M. Ogino, T. Naruke, T. Hoshika, T. Miyano, and K. Tsuneoka

3rd Department of Internal Medicine, Nippon Medical School, Tokyo, Japan Changes in transmucosal potential difference of the stomach (PD) may reflect active transport of ions across the mucosa at the gastric acid secretion, or injury potential at mucosal damage. We have investigated PD under endoscopic control. Method; The gastric electrolyte bridge was a polyethylen tube filled with 3.33 N. solution of K CL 3% agar. Placement of the bridge and subsequent verification were made under endoscopic control. Using skin (finger) as the site of the reference electrode, the electrolyte bridge led to balanced Calomel half cells which were connected to potentiometer. Result: In patients with chronic gastritis PD ranged from 2.0 to 25.0 (av.15.8) mV in fundic gland area, and from 17.5 to 45.0 (av. 31.3) mV in pyloric gland area (mucosal negative). In patients with gastric ulcer there was significant decrease of PD at the basis of ulcer and the mucosal fold surrounding the basis of ulcer where mucosal membrane assumed hyperemic and swollen, compared with adjacent mucosa. However, PD at the scar was about as equal as surroundings. Though it requires luther examinations as for the method and the condtions in the mucous membrane, we wish to put into practice for recognition of the atrophic border, guide to treatment of gastric ulcer, and differential diagnosis of benign and malignant lesions.

202

Proceedingsof the 58th AnnualMeeting, 1972-- Tokyo--(H) (196) G A S T R O I N T E S T I N A L DIVERTICULA: REPORT OF 54 CASES

S. Kitajima, I. Nakada, Y. Sasamori, H. Munakata, K. Tanaka, H. Oguro, T. Numata, and K. Oh-Uti

Department of Surgery, Faculty of Medicine, Hirosaki University, Hirosaki (Director: Prof. K. OH-UTI) Fifty five cases of the gastrointestinal diverticula were admitted in our clinic for the last twenty years. Their details were as follows : 14 cases of the esophagus, 1 of the stomach, 29 of the duodenum, 1 of the ileum, I of the Mechel's diverticulum and 8 of the large bowel. Esophageal diverticula: Most of the cases were found of the midesophagus. Two cases of the giant diverticulum and 2 cases with esophagobronchial fistula were also observed. Duodenal diverticula: H a l f cases accompanied with biliary diseases including cholelithiasis. Multiple diverticula were found in 6 case (20.7%). Diverticula of the large bowel: Most of the cases were found among male of 50 years and upward. Compared with the upper gastrointestinal tract, the cases of severer diverticulitis were observed in the large bowel. Two cases showed massive bleeding and one case had perityphilitic abscess. (197) E F F E C T O F A L C O H O L ON INTESTINAL DISACCHARIDASE ACTIVITY Y. Yoshida, S. Goto S. Yanagiya, K. Takashina, and F. Matsunaga

The 1st Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan and G. Sasaki

Department of Internal Medicine

Noshiro-Minsei Hospital Noshiro, Japan In order to study the roll of environmental factors in the etiology of adult lactase deficiency, alcohol effect on intestinal disaccharidase activity was studied in both clinical cases and experimental animals. Enzyme assay was done by Dahlqvist's method in the biopsied materials from the upper jejunal mucosa. Disaecharldase activities were as follows: lactase 6 . 6 • units, maltase 305.6• units, sucrase 106=~37.2 units in 17 alcohol drinkers, and lactase 6.34-3.7 units, maltase 259.1~79.4 units, sucrase 94.1=b35.7 units in 52 non-drinkers. Enzyme activities were somewhat higher in alcohol drinkers than in non-drinkers. T h e same tendency was observed in various digestive diseases, namely in peptic ulcer, port-gastrectomy, hepatic diseases, and irritable colon syndrome. Wistar rats were fed with alcohol ( 1 0 ~ 2 0 ml. of 20% ethanol/rat/day), and the disaccharidase activity were assayed with passage of time. Lactase, maltase, sucrase began to increase in activity after 2 weeks, and were definitely elevated after 6 weeks in comparison with the rats on normal diet. However, after 8 to 12 weeks the elevated activities gradually returned to the original level. It was concluded t h a t alcohol did not depress the intestinal disaccharidase activity but it might rather increase the activity in a certain period of time during alcohol intake. (198) S T U D I E S O N M I L K INTOLERANCE, WITH SPECIAL REFERENCE TO EVALUATION OF SERUM GALACTOSE LEVEL ON LACTOSE TOLERANCE TEST (LTT) W I T H E T H A N O L A. Kimura, T. Sasagawa, G. Takahashi, and H. Sugiyama

Division of Internal Medicine, Nagaoka Chuo-sogo Hospital In an effort to improve the reliability of the lactose tolerance test in the detection of

Proceedingsof the 58th Annual Meeting, 1972--Tokyo--(H) lactose deficiency, blood galactose and glucose levels were measured after the oral administration of lactose (20gm.) with ethanol, and, glucose and galactose (1:1, each 10gm.) with ethanol. The concentration of blood sugar was measured by autoanalyzer. The concentration of galactose was measured by galactose-oxidase method (Galactostat, products of Worthington Biochemical Corp., was used.). About the dosis of ethanol, which blocks the intrahepatic conversion of galactose to glucose, we tested 0.3, 0.2, 0.15 and 0 ml./kg, body wt.. It is concluded that 0.2ml./kg. of ethanol is minimal sufficient and clinically convenient dosis. The addition of ethanol caused a slight increase in blood glucose concentration. Fasting blood galactose was always 0-2.5 mg./dl.. Galactose and glucose tolerance test caused 14-27mg./dl. of increase at maximum in blood galactose in normal adult (30 or 45 rain. after administration). Twenty gram of lactose with 0.2ml./kg. body wt. of ethanol were administrated to 20 subjects. All cases whose intestinal mucosal lactase activities were lower than 1 unit/gm, wet wt. showed the rise in blood galactose less than 5mg./dl.. It is concluded that this technique would discriminate between normal and lactase deficient patients. Further examination, especially in white people, should be required. And, it is proposed that a single or twice blood galactose measurement after a small lactose-ethanol cocktail can be used as a screening test for Iactase deficiency. References

1) 2) 3) 4)

Fischer W. Zapf J.: Klin Wochenschr. 43: 1243-1246, 1965 Hjelm M.: Clin Chim Acta 15: 87-96, 1967. Kern F.Jr Heller M.: Gastroenterology 54." 1250, 1968. Isokoski M. Jussila J. Sarna S.: Gastroenterology 62: 28-32, 1972. (199) FUNDAMENTAL AND CLINICAL STUDIES OF SMALL INTESTINAL BIOPSIS. (VI) DIS-

203

ACCHARIDASE A C T I V I T Y AND LACTOSE TOLERANCE TEST K. Iwaki, S. Okada, H. Koizumi, M. Iwasaki, Y. Kawashima, H. Kaneda, K. Takahashi, T. Honda, and K. Ariga

The III Dept. of Medicine Nihon University It is very important problems for the clinical study correlating between biospy specimens of small intestinal mucosa and absorption of nuctritive substances. We have studied (1) the opinionare from the patient with milk intolerance, (2) Clinical study of lactose tolerance test, (3) disaccharidase activity from small intestinal biopsy and (4) change of component of food. The frequency of milk intoleranc was 17.3% of 1.477 cases. Although this cause was reported as lactase deficiency, it is presumed those were included in some factors after taking milk. This lactase enzyme is considered adaptation enzyme resulting from disaccharidase of small intestinal mucosa, abstinence of food, recovery of lactose tolerance with animal test. Milk intolerance cases were high incidence in surgical stomach. We are considering these etiology due to deficiency of lactose 1 and lactose 2. (200) DISACCHARIDASE ACTIVITY IN THE SMALL INTESTINE BY ENDOSCOPIC BIOPSY Woo pak Sa, H. Hozawa, and H. Hiratsuka

Hiratsuka Gastroenteric Hospital, Tokyo, Japan We carried out direct endoscopic biopsy of the gastrointestinal tract by the flexible intestinal fiberscope and spoke the results of disaccharidase activity. Method: 1) We used about 3 meter intestinal fiberscope (Type FIS-IIIb, Machida, Tokyo).

204

Proceedingsof the 584hAnmtal Meeting, 1972--Tokyo--(H)

2)

By means of a transintestinal tube the instrument was introduced perorally into the gastrointestinal tract and endoscopic biopsy was m a d e on the voluntary portions of the gut. 3) We measured disaccharidase activity by Dahlqvist's method. The measured enzymes are lactase I, Lactase II, Sucrase, and Maltase. Conclusion : l) It is not difficult and safe to introduce the endoscope with the help of intestinal string. But the preparation is complicated and the view in the gastrointestinal tract is limited because the gut is shortened with it. As compared with blind biopsy, endoscopic biopsy is profitable that we can gain the specimens of the bowel every time, confirm to stop bleeding and carry out voluntary parts of the intestine. 2) As the results of our data, disaccharidase activity were settled generally in homogenates of the j e j u n u m and ileum except that they seemed toward weaker in the terminal ileum. 3) One technician assayed enzyme activity of two or three specimens from the same part of a patient. Disaccharidase activity showed difference. We must re-examine the method of enzymatic assay. (201) E N Z Y M E A C T I V I T I E S O F JEJUNAL MUCOSA OF RATS WITH EXPERIMENTAL BLIND LOOP T. Susuki, Y. Kato, T. Mizuno, H. Oya, S. Yoshino, and T. Hattori

First Department of Internal Medicine, Nagoya University School of Medicine It has been well established that ERRATA:

blind

loops cause malabsorption and that some diseases with malabsorption show lowered activities of enzymes of small intestinal mucosa. This report concerns with the activities of enzymes of jejunal mucosa in experimental blind loop syndrome of the rat. Adult white male rats of Wistar strain weighing 200 to 250 Gm. were used. Filling blind loops, 10 cm in length and 40 cm proximal to the cecum, were constructed in rats according to the method described by Cameron. A month after the operation measurement of fecal fat and activities of enzymes of rat jejunal mucosa, i.e., alkaline phosphatase, leucine aminopeptidase and disaccharidases (lactase, sucrase and maltase) were carried out. Fecal fat for 3 days was 0.92• (mean 4-S.D.) Gm. in the operated and 0.294-4-0.18 Gm. in control rats. Lactase activity was inversely related to fecal fat. The activity was 9.34-2.5 u./Gm, protein in rats with blind loop and 18.3• protein in controls. There was no significant difference between the two groups in activities of the other enzymes. The operated rats showed an abnormal proliferation of flora in the hypertrophied and dilated blind loop filled with ehyme. In the present study lactase was found to be the only enzyme whose activity was affected in association with the increase in fecal fat. It can be assumed that the functional disturbance in the cells of small intestinal epithelium evidenced by reduced lactase level results in steatorrhea. Further study is required to elucidate whether the functional disturbance of small intestinal mucosa is caused by an abnormal proliferation of flora or not, and whether that is the cause of steatorrhea or the result of malabsorption.

Previous number, Vol. 8, No. 1, 1973. error

page 27, line 3: page 38, line 2:

ANOBSERVATION CLINIDAL

correct

AN OBSERVATION CLINICAL