Mitsuru Konn

Late development of bile duct cancer after sphincteroplasty: A ten- to twenty-two-year follow-up study☆

BACKGROUND Transduodenal sphincteroplasty is designed to destroy the sphincteric muscle fibers, producing a terminal choledochoduodenostomy. In the absence of Oddis sphincter, intestinal contents with both activated pancreatic juice and bacterial flora are refluxed into the bile duct and remain there for a prolonged time. The long-term effect of producing the reflux has not been evaluated to date. METHODS One hundred nineteen consecutive patients undergoing transduodenal sphincteroplasty between February 1973 and July 1984 were included in this study. Postoperative clinical courses of 108 patients could be evaluated by means of a retrospective review of the hospital records. Median follow-up was 18 years. RESULTS Eight cases (7.4%) of primary bile duct cancer were found among the 108 cases at intervals of 1 to 20 years after sphincteroplasty. Two patients had concurrent hepatolithiasis. The patency of sphincteroplasty was confirmed in all cases, and the bile was infected in seven cases. Pathologic specimens obtained demonstrated cholangiocarcinomas and various degrees of atypical hyperplastic lesions under the background of chronic cholangitis. CONCLUSIONS Chronic cholangitis can be an important causative factor in late development of bile duct cancer after sphincteroplasty. Any patients treated with choledochoduodenostomy should be closely monitored for late cholangiocarcinoma.

Survival and recurrence after low anterior resection and abdominoperineal resection for rectal cancer: the results of a long-term study with a review of the literature.

Morbidity, survival, and recurrence in 203 patients treated with curative low anterior resection (LAR) were compared with those in 100 patients treated with curative abdominoperineal resection (APR). The overall 5-year survival figures for the total number of, LAR and APR patients were 75.6±5.7%, 79.8±6.4% and 67.7±9.6%, respectively. The prognosis for cancers situated low enough in the rectum to involve the anal canal was poor even when managed by APR, as evidenced by a low survival at 5 years of 59.0±9.6% and a high pelvic recurrence rate of 34%. For all except these tumors, LAR proved at least equal to, or better than APR as a curative surgical method for middle and low rectal cancers, on the basis of 5-year survival being 79.8±6.4% vs 78.7±5.2%, operative mortality being 1.5% vs 1.0%, morbidity being 39.4% vs 59.0%, and the incidence of pelvic recurrence being 8.9% vs 13.5%. When deciding upon the most appropriate surgical procedure for rectal cancer, especially for middle or low rectal lesions, the patient should not simply be condemned to a permanent colostomy. Thus, we first attempt LAR for every lesion except those which are very advanced or those with anal canal involvement, if technically feasible and suitable for the individual patient.

Regurgitant bile acids and mucosal injury of the gastric remnant after partial gastrectomy

Three groups, each consisting of seven patients who had undergone either Billroth I, Billroth II, or pylorus-preserving gastrectomies, were evaluated more than 18 months postoperatively in terms of concentration and amount of bile acids in the gastric aspirate and histologic changes in the gastric remnant mucosa. Concentrations of bile acids were determined by gas chromatography and mucosal specimens were obtained by endoscopic biopsy. The total bile acid concentration and all of the individual fractional bile acid levels, whether free or conjugated, were significantly higher in the Billroth II group than in the other two groups. The amount of gastric aspirate was also highest in the Billroth II group. Endoscopic biopsy revealed glandular dysplasia to be predominantly in the Billroth II group. The presence of bile acids in the gastric remnant may contribute to mucosal injury, possibly leading to cancer in the gastric remnant, especially after the Billroth II operation.

The effects of intraportal prostaglandin E1 administration on hepatic warm ischemia and reperfusion injury in dogs.

To determine the route of prostaglandin E1 (PGE1) administration which would have the greatest protective effect against hepatic warm ischemia, two experiments were performed using dogs. The pharmacokinetics of PGE1 were investigated in a preliminary study, after which, the effects of PGE1 in a 90-min warm ischemic liver model were examined. The dogs were divided into three groups of ten, according to the treatment given: group A was an untreated control group, group B received PGE1 intravenously, and group C received PGE1 intraportally. The PGE1 was infused continuously at a rate of 0.02 μg/kg/min before and after ischemia. All the dogs in groups A and B died within 24 h of induced ischemia. Whereas, six of the ten dogs in group C survived for over 3 days. The arterial ketone body ratio was not maintained in groups A and B, but it was in group C. Furthermore, in group C the serum lipid peroxide level, which reflects hepatocellular membrane damage, was maintained at a lower level than that in the other groups after ischemia. Electron microscopy revealed sinusoid destruction and changes in both the plasma membrane and parenchymal cell mitochondria in groups A and B, while in group C these structures were well preserved. These findings confirmed that intraportally administered PGE1 improved the hepatic microcirculation and stabilized the hepatocellular membranes. Our results indicate that intraportal administration of PGE1 has a greater protective effect than intravenous administration against warm ischemic liver injury.

Postoperative abnormal prothrombinemia in patients with cefoperazone: report of two cases.

N-methyl-thio-tetrazol side chain should thus be used with particular prudence in patients with abnormal prothrombinemia and a tendency to develop bleeding disorders.

Characterization of glycosaminoglycans in regenerating canine liver

BACKGROUND/AIMS Liver regeneration after partial hepatectomy is accompanied by hepatocyte proliferation and alteration of the extracellular matrix. Glycosaminoglycans, which are components of the extracellular matrix, interact with other matrix components, and are related to hepatocyte growth. The aim of this study was to investigate the relationship between hepatocyte proliferation and changes in glycosaminoglycan. METHODS Hepatocyte proliferation and changes in glycosaminoglycan were investigated in dogs after 55% partial hepatectomy. Hepatocyte mitosis was investigated by immunohistochemistry using anti-proliferating cell nuclear antigen antibody. The amount of glycosaminoglycan was determined by the carbazole-sulfuric acid method. We used a new method for analysis of glycosaminoglycan chains, involving endo-beta-xylosidase digestion and fluorescence labelling, to investigate the components of glycosaminoglycan. RESULTS Hepatocyte mitosis was increased after hepatectomy, reaching a peak at postoperative day 7. The total amount of hepatic glycosaminoglycan reached a maximum at 1 to 2 weeks afer hepatectomy, and the ratio of the components showed a concomitant change, the amount of heparan sulfate increasing, and that of chondroitin sulfate/dermatan sulfate decreasing. Increased heparan sulfate has shorter chains at 1 to 2 weeks after hepatectomy. CONCLUSIONS These results suggest that the transient changes in heparan sulfate with a decreased chain length and chondroitin sulfate/dermatan sulfate and observed during liver regeneration are associated with hepatocyte proliferation.

Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from human pancreatic juice

SummaryHuman pancreatic juice, obtained from nine patients after partial excision of the pancreas for bile duct cancer, was fractionated in order to isolate its glycopeptides. Three glycopeptides were purified employing ion-exchange chromatography and gel filtration. All the glycopeptides were found to be free of sialic acid and galactosamine but to have an unusually high content ofl-fucose. The chemical structures of the three glyco-peptides were determined using 500-MHz [1H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary structure with threel-fucose residues. The second glycopeptide, GP-3, had a triantennary structure with fourl-fucose residues, and the third one, G-2, had a tetra-antennary structure with fivel-fucose residues. The chemical compositions of these glycopeptides, including the absence of sialic acid and the highl-fucose content, indicate that they represent a new class of glycopeptide present in the normal human pancreas.

Enzymic determination of acidic glycoconjugates in human pancreatic juice

SummaryAcidic glycoconjugates (glycosaminoglycans, sulfated glycopeptide, and sialoglycopeptide) were isolated by precipitation with cetylpyridinium chloride from human pancreatic juice after digestion with pronase. The acidic glycoconjugates were found exclusively in the proteinaceous precipitate that occurred during dialysis against a buffer of low ionic strength. The concentration of the acidic glycoconjugates in normal pancreatic juice was about 2.4 mg/L. The acidic glycoconjugates were characterized by electrophoresis on cellulose acetate membrane and chemical analysis before and after digestion withStreptomyces hyaluronidase, chondroitinase AC, chondroitinase ABC, and heparitinase. It was found that the major acidic glycoconjugates were heparan sulfate (39.3%), sulfated glycopeptide (34.4%), chondroitin sulfate (14.2%), and the minor ones hyaluronic acid (6.4%) and sialoglycopeptide (5.7%).

The effect of intraportal PGE1 on warm ischemic liver damage

To determine the most effective route of administering prostaglandin E1 (PGE1) to inhibit warm ischemic liver damage, 90-min warm ischemia was established in a canine model. The dogs were divided into three groups according to the treatment given. Thus, group A (n = 10) was the control group which received no treatment, group B (n = 7) was administered PGE1 intravenously, and group C (n = 7) was administered PGE1 intraportally. PGE1 was continuously administered before and after the ischemia at a rate of 0.02μ⦰/min. The branched-chain amino acid to aromatic amino acid ratio in the hepatic vein, and the arterial ketone body ratio of acetoacetic acid to β-hydroxybutyric acid, were examined to observe the metabolism of each amino acid and the oxidation-reduction ability of hepatocytes. Both ratios were maintained only in the group C dogs, three of which survived for over 3 days, whereas in groups A and B, all the dogs died within 24h. The results of this study imply that the intraportal administration of PGEI was more effective against warm ischemic liver damage than the intravenous administration of PGE1.

Possible role of hepatic bile mucus glycoprotein in development of intrahepatic gallstones

To study the role played by hepatic bile mucus glycoprotein in the development of hepatolithiasis, mucus glycoprotein, isolated from the bile of patients with intrahepatic gallstones by gel filtration and ultracentrifugation, was examined for precipitability in control hepatic bile obtained postopertively from patients successfully treated for cholecysto-and/or choledocho-lithiasis. When the mucus glycoprotein was incubated at 38°C for 48h in the control hepatic bile in the presence of calcium inons, massive precipitation was produced. The precipitation was inhibited by treating the mucus glycoprotein with acid, alkali, a reducing reagent, or protease, the inhibition being most effective with acid, which splits up carbohydrate chains. This suggests that the precipitability of the mucus glycoprotein resides mainly in its carbohydrate chains. These observations imply that the development of intrahepatic gallstones, calcium bilrubinate stones in particular, could be prevented by degrading mucus glycoprotein in hepatic bile.