I have been studying the pathophysiology of chronic pancreatitis over a long period, discussing it with particular reference to the clinical aspect of the correlation between the stomach and the pancreas. When the correlation between the stomach and the pancreas was looked upon from the standpoint of the secretion of gastric juice and that of pancreatic juice, with particular reference to the acid and bicarbonate secretions, it was found that the secretions of the two juices in normal subjects were in positive correlation, and the findings were described in a previous paper.
It was, in fact, of particular interest that when the patients with chronic pancreatitis and those with recurrent chronic pancreatitis according to the diagnostic criteria were examined for their A/B ratios, many patients were classified into type III and type I.
It was further interesting that there were some extraordinary types of chronic pancreatiti including one patient (with recurrent gastric ulcer) from type I in whom the autoimmune mechanism was pathologically considered, a few patients presenting paradoxical blood gastrin secretion observed in cases of Zollinger-Ellison syndrome, and one patient in whom the proliferation of Langerhans' islets (tumor?) was demonstrated.
The fact that the administration of secretin led to improvement may be suggestive of the existence of a secretin abnormality in the pathogenesis, though it is not clear at what level of the metabolic process (synthesis, secretion, receptor, elimination, etc.) this abnormality exists. It would also be possible to understand this abnormality in terms of “relative shortage”, since the addition of secretin led to improvement. One piece of evidence that might support this possibility is the fact that chronic pancreatitis is caused by difficulties in outflow of pancreatic juice due to the structural defect. In other words the disease may be described as a state of impeded outflow of pancreatic juice due to a relative shortage of secretin. Under this condition, the body's response should naturally be one of increased secretion of secretin. However, it seems that such a phenomenon does not readily occur in reality. Presumably, this is due to the fact that the body must take time for such an in adjustment.
It takes many years before pancreatitis becomes stabilized. Furthermore, secretin levels tend to be high among the stabilized type of pancreatitis (our type III). However, it should be emphasized that the cases analyzed in this study belong to type I. which show low secretin values. Needless to say, it is type I chronic pancreatitis that has the many clinical problems. Thus, the secretin wash-out method is a therapy ideal for the purpose.
Although more cases have to be accumulated, the Δ substance p/Δ enkepharin (Met) ratio fluctuates interestingly in a small number of cases with severe pain. This is a clinical subject that needs further studies. Particularly, it is of great significance that the possibility of a subpathway via blood other than the main pathway being mobilized at the time of surgical invasion of the living body was suggested clinically.
This therapy which we have developed is worthy of note in that it has successfully shortened (to 5 years or less) and stabilized the treatment of chronic pancreatitis, which normally takes many years (perhaps 10 years or more). However, it is known that pain disappears spontaneously in some cases of chronic pancreatitis. Therefore, we think we must conduct various studies in reference to the “burn-out” suggested by Ammann, Gastard's report, and important surgical indications described by White, with or without calcification, whether or not alcohol is taken, and in consideration of heredity, race, diet, environment, and other background factors.

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This investigation was undertaken to evaluate thyroxine-binding globulin (TBG) as a marker of liver metastasis. Studies were performed on 50 post-operative patients with liver metastasis. Diagnosis of liver metastasis were done by liver scintigram, CT scanning, uitrasonography, or surgery. For the comparison, 42 primary hepatoceliular carcinoma, 19 post-operative patients with bone metastasis, and 33 follow-up patients with chronic liver diseases were also studied. None of these patients had had a history of thyroid disorders or ever received estrogen therapy. Serum was collected just before the injection to obtain the relevant scintigram by 99m-Tc-phytate. TBG was assayed by using the manufacturer's protocol. All patients underwent thyroid function studies. Both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were obtained within the same period.
In our examination, TBG was significantly higher than normal in spite of euthyroid state when the patient had the liver metastasis, whatever the primary site of the tumor or its histological findings. Of 50 patients with liver metastasis 36 patients (72%) showed a higher TBG, from 28.8 to 49.4 μg/ml. Among 42 patients with primary hepatocellular carcinoma, 29 (69%) had a higher TBG. CEA was negative in 18 patients with liver metastasis. But 14 of these patients showed a higher TBG. On the other hand, TBG was almost normal in patients with bone metastasis and of various concentrations in chronic liver diseases.
We conclude that elevated TBG is a sensitive, fairly reliable, nonspecific tumor marker to determine liver tumors, especially in cases of liver metastasis.

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Since 1980, serum alpha-fetoprotein (AFP) level was measured in 233 patients with hepatocellular carcinomas and chronic liver disorders by radioimmunoassay methods. The patients of hepatocellular carcinomas were divided into two groups. Namely, one group showed high level of AFP (≥200 ng/ml) and the other group showed low level of AFP (<200 ng/ml). Some of chronic liver disorders (without hepatocellular carcinoma) also showed high level of AFP.
It was necessary to differentiate hepatocellular carcinomas from benign liver diseases. From this points of view, we set up reference values of liver function tests and tumor marker tests as below:
GOT/GPT≥2, ALP≥20 KAU
LDH≥450 mIU, ICG (K)≤0.05
Ferritin≥200 ng/ml, beta 2 microglobulin≥10 ng/ml
In conclusion, in high levels of AFP, hepatocellular carcinomas are suggested when the data of liver function tests and tumor marker tests are in the range of reference values.
And also, in the cases of AFP, when the data of liver function tests and/or tumor markers are in the range of reference values, the cases suggest hepatocellular carcinoma.
On the contrary, even though alpha-fetoprotein level shows high value, hepatocellular carcinoma may be ruled out when these data of liver function tests and/or tumor marker tests are not in the range of reference values, namely, the case suggests benign chronic liver disease.

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Hepatitis B surface antigen (HBs Ag) carriers were examined by peritoneoscopy and their liver surfaces were analysed according to their age, clinical course (including the alanine aminotransferase (GPT) activities) and hepatitis Be antigen (HBe Ag). The liver surfaces were classified into 4 surface codes, “100”, “200”, “300” and “400”, according to Shimada's classification.
In HBe Ag positive carriers, those of forty years and over had irregular or nodular liver surfaces (“300” or “400”). Whereas those of less than forty years had more smooth liver surfaces (“100” or “200”). These data suggest that the liver surface changes gradually and progressively with the age in HBe Ag positive carriers.
On the contrary, some of those of HBe Ag negative carriers with more than forty years remained in smooth liver (“200”) without any clinical symptoms. Most of the carriers in “300” group, whether they were positive for HBe Ag or not, showed reddish-brown patches, which suggested that the liver changed progressively. We conclude that the seroconversion from HBe Ag positive to negative in the earlier stage (less than “300”) is indispensable.

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Carcinoembryonic antigen (CEA) was measured in serum and bile in patients with benign and malignant biliary tract diseases.
Serum CEA level was significantly high in gallbladder cancer alone but was found to be a poor diagnostic marker for early cancer.
Gallbladder bile CEA level was also much higher in gallbladder cancer (mean 8116.3 ng/ml) and in stage I cases who were operlted on curatively, bile CEA level was 7361.6 ng/ml.
Hepatic bile CEA level was higher in bile duct cancer (mean 423.4 ng/ml) compared with in cholelithiasis (mean 3.5 ng/ml) and in gallbladder cancer (mean 37.3 ng/ml).
Hepatic bile CEA level was elevated in malignant obstructive jaundice but was decreased immediately following relief of obstruction.
During obstructive phase, bile CEA in malignant diseases were elevated but were not elevated in benign diseases.
This finding is useful to differentiate benign from malignant diseases in obstructive jaundice.

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Inner biliary fistula, which is one of the complications of cholelithiasis, is a relatively uncommon disease. We reported 3 cases of biliobiliary fistula, which were very rare.
They were two women and one man. The age ranged from 40 to 62 years. The chief complaint was jaundice or pain, while all three cases showed jaundice. There were pain in 2 cases; fever in 2 cases, while no symptoms of shock or disturbances of consciousness were seen. The symptoms lasted for over one year in all three cases and more than five years in 2 of them. Before operation, accurate diagnosis of biliobiliary fistula was made in one case, while in the other two cases, tentative diagnosis of choledocholi-thiasis or gallbladder stone with Mirizzi's syndrome was made. The diagnostic method was either echogram or cholangiogram by PTC or PTBD. The fistula were Corette type I in 3 cases.
The basic operative methods consisted of cholecystectomy, lithotomy, construction of biliary duct or drainage from biliary tract. However, a large defect in the right side of the bile duct was made after removal of the large stone existing both at hilus of gallbladder and common hepatic duct or choledochus. Since the biliary tract with stone was surrounded by inflammatory changes and was fragile, it was often difficult to make the reconstruction of the biliary tract. For these reasons, incision or removal of the gallbladder or the bile duct should be performed after deciding the operative method carefully, and unreasonable cholecystectomy or the reconstruction of the biliary tract should be avoided. We consider that in these patients, the construction of the biliary tract using patch graft and effective biliary drainage after removal of stone are best operative methods.

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Glaidia lamblia has a world-wide distribution and lives in the small intestine, especially in the duodenum and occasionally in the gall bladder of man. Severe infection with G. lamblia may cause edema of the ampulla of Vater, cholecystitis or gastro-intestinal symptoms.
Recently the authors experienced two cases of G. lamblia infection in Aomori Prefecture which caused biliary disorder.
Case 1: A 41-year-old male farmer. He complained of epigastric pain with nausea and vomiting. A lot of trophozoite of G. lamblia was detected from the duodenal juice. He was treated by chloroquine and no protozoa were found after the administration, 750 mg per day for 5 days.
Case 2: A 52-year-old male barber. He complaind of epigastric pain and a lot of G. lamblia trophozoites were found from the duodenal juice. As a treatment, 1.0 g of sigma-mycin was administered for 6 days, and he was successfully treated.
These two cases are thought to be infected in Japan, but Giardia lamblia infection are being imported more frequently as many people in tropical areas either enter or return to Japan. Therefore, the attention should be paid for the G. lamblia infection.

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In October 1979, the liver surgery group of National Cancer Center began to perform the ultrasonically guided systemic subsegmentectomy of the liver for hepatoma with liver cirrhosis. Recently many surgeons perform this method.
In March 1984, we had a case of hepatoma with liver cirrhosis which was well localized in the anterior-superior subsegment of the right lobe. So we performed the ultrasonically guided systemic subsegmentectomy of the liver for this case. The post-operative course of this case was good and one month after the operation the patient's general condition was good.
We think that in the future we will perform this method for hepatoma with liver cirrhosis which is well localized in the subsegment of the liver.

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Pulmonary hypertension (PH) is a rare con7plicaticn of liver cirrhosis. We report a case of liver cirrhosis in which PEI occurred during a period of follow-up observation.
A forty-nine year old male who was positive to HBs-Ag in 1979 developed hepatic encephalopathy and he was admitted to our institution in Dec. 1983.
Chest X-ray film on admission revealed dilated proximal part and narrowed peripheral partof pulmonary artery. ECG showed right ventricular strain pattern. Phorocardiogra-phycally, IIp was accentuated. Lung scintigram showed bilateral central hilar low activity.
Echocardiogram showed dilated right ventricular cavity, hypertrophy of the right ventricular wall, and right ventricular strain pattern. Cardiac catheterization showed increased pulmonary artery pressure and pulmonary artery pressure resistance index, 70/25 mmHg, 1648 dyne·sec·cm^-5/m², respectively.
Although there are several explanations for the relationship between liver cirrhosis and PH, it is still unknown.

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Recently an administration of interferon or transfer factor (TF) to HBs antigen positive chronic hepatitis (hepatitis B) in children has been attempted, but an application of administration of adenine arabinoside (Ara-A) and TF is rare in children. We tried to use Ara-A and TF in a 13-year-old boy who was given blood transfusion for the treatment of burns at the age of 2 and later developed active hepatitis B. We administered Ara-A dissolved in 500 ml of 5% glucose solution to him by drip infusion over 4 hours for 7 days at a dose of 8.5 mg/kg/day and for 23 days at a dose of 5 mg/kg/day, and a total dose of 6, 240 mg of Ara-A was administered for 30 days. Twenty-five days later same dosage of Ara-A was administered to him in the same way. Furthermore, 25 days later same dosage of Ara A was repeated together with a total of 5 pack of half a unit of TF (Hokkaido Red Cross Blood Center) once a week by intracutaneous injection. By the administration of these drugs, serum GOT, GPT, TTT, ZTT and LDH of the patient became normalized, and serum γ-GTP decreased gradually. Also HBe antigen became negative, HBe antibody titer was elevated and DNA-polymerase were normalized The serum HBe antigen was increased transiently, but this phenomenon might show that the destruction of infected hepatic cells by activated lymphocytes was occurred. There were no side effects by the administration of these drugs, so this method seemed to be very useful in children with hepatitis B.

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