Based upon the findings obtained by esophageal radiological examinations, esophagoscopies and manometric studies, for sliding esophageal hernia, attempts were made to revise diagnostic criteria and classifications, which were then applied clinically. The mucosal esophagogastric junctions by endoscopy coincide well with the muscular esophagogastric junctions in X-ray study in 85.7% of the cases and with the lower esophageal sphincter in manometric study in 77.1%, which made us believe the mucosal junction, muscular junction and LES situate in the identical region. The newly established endoscopical and radiographical classifications showed good correlation in more than 70% of the cases. Esophageal manometric study showed that significantly elongated high pressure zone in hiatal hernia had double peaks in 81.5% of the cases, and that only its oral peak responded to gastrin administration (4, μg/kg). With wider clinical application of new criteria and classification, the incidence of hiatal hernia in Japan has been found to be 17.8%, and it increases with aging. There appears no difference in sex distribution. Reflux esophagitis is observed quite frequently among the patients with hiatal hernia.
Clinical investigation of group I pepsinogen (PG I) was carried out by PG I radioimmunoassay kit (Midori Juji). The mean (±SEM) levels of PG I in 318 healthy subjects was 79±3ng/ml. Mean serum PG I for the men in this population, 87ng/ml, was significantly greater than the value for women, 72ng/ml. Serum PG I levels in patients with gastric ulcer, and duodenal ulcer were 91±7ng/m1, 117±l0ng/ml, respectively, and both values were significantly greater than the value in subjects with endoscopically normal gastric mucosa, 63±5ng/ml. No significant change in serum PG I was observed after subcutaneous injection of tetragastrin or meal ingestion. A significant correlation was found between serum PG I and stimulated pepsin output (S.P.O.), peak pepsin output (P.P.O.), maximal acid output (M.A.O.), peak acid output (P.A.O.), which suggests that the level of serum PG I may be determined by chief cell mass.
Studies were performed in Tomie Town, Nagasaki Prefecture where the mortality rate of liver cirrhosis is 26/100, 000. Thirty two patients with chronic liver diseases diagnosed by liver biopsy were followed for 1 to 10 years and the histological findings of the second biopsy specimens were compared to the initial diagnosis. At their first visits, patients were consisted of 4 cirrhotics, 7 with chronic active hepatitis, 2 with chronic inactive hepatitis, 14 with liver fibrosis, 2 with fatty liver, 2 with intrahepatic cholangitis and 1 with nonspecific reactive hepatitis. The histological diagnosis of the second biopsy specimen was same as the initial diagnosis 32 patients but 10 patients showed different histological findings from those obtained from the first biopsy. Hepatoma was developed in 4 patients; 3 from patients with liver cirrhosis and 1 from chronic active hepatitis. These 3 cirrhotics had HBs antigen and a patient with chronic active hepatitis had HBs antibody. Liver cirrhosis was developed in 2 patients with chronic active hepatitis who were HBs antigen carriers. Chronic inactive hepatitis was newly found in 3 patients, 1 from patients with chronic active hepatitis and 2 from liver fibrosis. A patient with chronic active hepatitis at his first visit showed liver fibrosis at the second biopsy. These results suggest that hepatoma as well as liver cirrhosis develope mainly from chronic hepatitis, type B, at least in Tomie-Town, Nagasaki Prefecture.
The antibodies which react with Chang liver cell membrane were detected in the sera of 26 (58%) of 45 patients with alcoholic liver disease by radioimmunoassay using 125I protein A and the antibody dependent cell-mediated cytotoxicity (ADCC) against Chang liver cell was demonstrated in the sera of 11 (38%) of 29 patients. There was a close correlation between the presence of antibody and the ADCC. Moreover the ADCC has been shown to be mediated by the anti-Chang liver cell membrane antibody. There was also a close association between the presence of the anti-Chang liver cell membrane antibody and the degree of a lymphocytic infiltration in the portal tracts on liver biopsy, a characteristic finding seen in an autoimmune disorder of chronic active hepatitis. It is suggested that the production of autoantibody to liver cell membrane may be important in the progression of alcoholic hepatitis to more advanced liver disease.
Various serum protein levels and values of dye excretion tests, which reflect total functioning hepatic cell mass, were determined in 99 cases of usual type of liver cirrhosis without hepatoma, to elucidate the role of these tests in assessment of prognosis in liver cirrhosis. Cumulative survival rates were calculated in two different groups which were devided according to the boundary value of each of these tests. The boundary value for each test was obtained by comparing the mortality rates for 3 years and by finding out the point where the mortality rates showed the gratest difference. Serum albumin and α 2-heat stable glycoprotein with relatively long turnover rate were the most useful in determining long-term prognosis of liver cirrhosis, and also useful for assessment of early prognosis. On the other hand, serum prealbumin with short turnover rate and ICG maximum removal rate were good indices to predict death with hepatic coma. Serum cholinesterase was useful both for assessment of prognosis and for prediction of hepatic coma.
Bile composition and lithogenicity were studied in 19 patients with ileocecal resection, 3 with ileostomy, and 7 with total colectomy combined with ileoproctostomy. Lithogenicity of bile was compared in a Thomas lithogenic index and on an Admirand-Small triangle, resulting in an increase of lithogenicity in patients with ileocecal resection and ileostomy. The ratio of glycine to taurine-conjugated bile acid (G: T ratio) didn't increase also in these patients. As for the percentage bile acid composition of bile, a decrease of deoxycholic acid was noted in each group. These results suggested that a risk of complicating cholelithiasis would be high after ileocecal resection and ileostomy.
With an end to characterize the mechanism of glucose intolerance during bile-duct obstruction, studies were carried out, as follows: 1) Clinically, patients with different liver disorders (obstructive jaundice, liver cirrhosis and chronic hepatitis) were subjected to oral glucose tolerance test (OGTT), and the responses of 30K-immunoreactive glucagon (IRG) during OGTT were studied. 2) In animal experiments using rabbits, percutaneous choledochoduodenal drainage was settled in animal models to find out the bearing of the status of bile inflow on IRG response during OGTT. Futhermore, the clearance rates of glucagon and insulin in the liver as well as the biliary levels of IRG and immunoreactive insulin (IRI) were determined in these animals. The findings are summarized, as follows: 1) All patients were hyperglucagonemic. However, the paradoxical response of IRG during OGTT could be observed in only those patients with obstructive jaundice. IRG detected in hyperglucagonemic patients with biliary stagnation was large molecular IRG. 2) In rabbits under obstruction of the common bile-duct, hyperglucagonemia and the paradoxical response of IRG during OGTT were noticed as in man. When the extracorporeal loop was opened, hypoglucagonemia was induced, but the IRG responce during OGTT was depressed. It was confirmed that the bile-duct is important metabolic pathway for glucagon and insulin, and that the biliary levels of IRG and IRI were approximately 200 times and 4 times the plasma levels, respectively. The above findings suggest that glucose intolerance during bile-duct obstruction is associated with hyperglucagonemia due to bile stasis which is characterized by high circulating levels of large molecular IRG.
The influence of obstructive jaundice on the pancreatico-trophic effect of trypsin inhibitor was studied in rats following laparotomy. The wet weight of the pancreas in rats treated with trypsin inhibitor was 1.6 times that of untreated rats, whereas in rats with obstructive jaundice, the weight in trypsin inhibitor treated animals was 2.2 times that of untreated animals. The protein content of the pancreas in treated rats was 2.4 times that of untreated, but was unaffected by obstructive jaundice. Obstructed rats treated with trypsin inhibitor showed a decrease in total amylase content of the pancreas and histologically a decrease in the zymogen granules of the pancreatic acinar cells compared with unobstructed treated animals. Obstructive jaundice significantly increased the pancreatico-trophic effect of trypsin inhibitor, and this may be due to a prolongation of effect of the pancreatico-trophic hormone(s) induced by trypsin inhibitor in obstructed animals.
The effect of bile on plasma immunoreactive secretin and pancreatic exocrine secretion were studied in dogs with pancreatic fistula. The mean plasma immunoreactive secretin was significantly elevated and volume and bicarbonate out-put of pancreatic juice significantly increased following bile infusion to the duodenum. The response of plasma immunoreactive secretin was related to a volume of bile infused to the duodenum. Those data indicates that the increment of volume and bicarbonate of pancreatic juice following bile infusion is mainly mediated by the release of endogenous secretin.