Shuji Tsuchiya

Randomized, controlled study on adjuvant immunochemotherapy with PSK® in curatively resected colorectal cancer

A randomized, controlled trial of adjuvant immunochemotherapy with PSK®(Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK®group received PSK®orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow-up time for this study was four years (range, three to five years). The disease-free survival curve and the survival curve of the PSK®group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival,P=0.013; survival,P=0.013). These results indicate that adjuvant immunochemotherapy with PSK®was beneficial for curatively resected colorectal cancer.

Effects of cyclosporin A on active Crohn’s disease

SummarySeven patients with active Crohn’s disease were treated with cyclosporin A orally for 16 weeks. The initial dose was 8 mg/kg/day and the subsequent dose was adjusted to maintain the plasma concentration of cyclosporin A of approximately 200 ng/ml. The mean value of the Crohn’s disease activity index before treatment was 194.3±57.4. It was gradually decreased reaching a nadir at 12 weeks (139.0±45.6, p< 0.05) and one enterocutaneous fistula was closed. White blood cell counts, hemoglobin and α-2-globulin did not significantly improve during treatment. Cyclosporin A could be indicated when steroids, sulfasalazine or azathioprine are not effective or not tolerated.

Pathogenesis and clinical features of acute cholangitis accompanied by shock

We investigated 91 cases of acute cholangitis, including 42 of severe cholangitis and 49 of mild cholangitis. The incidence of endotoxemia was 78.6 percent in 42 and 32.6 percent in the 49 patients. In the 42 with severe cholangitis, remarkable leukocytosis, thrombocytopenia, decrease of serum CH50, C3, plasma fibronectin and phagocytic index were characteristic. Disseminated intravascular coagulation (DIC) was observed in 76.2 percent. Since there was a positive correlation between platelet counts and levels of CH50 and C3, the decrease of platelet count, and the occurrence of DIC in patients with endotoxemia were thought to be closely related to the consumption of complements. There was no difference in mortality rate between nonsurgical treatment (57.8 percent) and the emergency bile drainage treatment (56.5 percent). The results of therapy depended on the degree of complicating DIC. We conclude that acute cholangitis was aggravated by endotoximia and that severe cholangitis was accompanied by DIC induced by a decline in phylaxis.

Human Monoclonal Antibodies against Cytokeratin 18 Generated from Patients with Gastric Cancer

By co‐culturing regional lymph node B‐cells and HAT‐sensitive mutant cells obtained from RPMI‐1788 cells, no less than 20,000 Epstein‐Barr (EB)‐transformed colonies were obtained from 32 patients with gastric cancer. From B‐cell cultures generating antibodies reactive with gastric cancer tissues as well as cultured gastric cancer cells, two EB‐transformed cell clones termed C418–59 and C1218–39 were isolated. Both of them produced human IgM‐class antibodies, termed Mab418–59 and Mab 1218–39, respectively. Both antibodies reacted with an antigen with a molecular weight of 45 kd existing in gastric cancer MKN‐45, MKN‐1, and Kato‐III cells, and also with all of 4 adenocarcinomas of the stomach in paraffin sections. The antigen recognized by both antibodies was identified as a kind of cytoskeletal protein, cytokeratin 18, In this study, it was confirmed that B‐cell clones generating autoantibodies against cytokeratin 18 were present in some patients with gastric cancer.

The medical, nutritional and surgical treatment of fistulae in Crohn's disease

Of a total 44 patients with Crohns disease, 10 patients with 9 internal and 15 external fistulae, some of which were recurrent, were analyzed at the Department of Surgery, Yokohama City University between 1973 and 1988. Twenty-two fistulae were treated with medical and nutritional therapy using either total parenteral or enteral hyperalimentation by which the closure rate of the internal and external fistulae was 0 (0/9) and 42 per cent (9/14), respectively. The nutritional status of all the patients with fistulae treated by nutritional therapy improved, especially those whose fistulae were closed. However, 8 of 9 internal fistulae and 5 of 15 external fistulae finally required resection of the fistula with the distal stenotic bowel segment. The re-opening rate of fistulae following successful medical/nutritional therapy and surgical therapy was 88.9 per cent (8/9) and 53.8 per cent (7/13), respectively, and the mean interval until recurrence was shorter in the patients who underwent medical and nutritional therapy (4.5 months) than in those who underwent surgical therapy (19.4 months). Thus, using medical and nutritional therapy, none of the internal fistulae were closed, but 9 of 14 external fistulae were. The optimal management of internal fistulae is therefore thought to be bowel resection to include the distal stenotic lesion, while medical and nutritional therapy is thought to be of value for external fistulae.

Primary cholesterol hepatolithiasis

SummaryStones extracted from patients with hepatolithiasis were analysed by infrared spectrophotometry. Cholesterol stones containing 70% or more cholesterol were found in 12 out of 55 cases. Judging from the lodging site of the stones, the degree of dilatation of the cystic duct, and the presence of cholecystitis, five of the cases were considered to be cholesterol stones produced in the liver. Two out of the five cases were a 44-year-old female and a 46-year-old female, respectively, with normal bifurcation of intrahepatic ducts, and stones were found in the lateral branches of dilated cystic bile ducts. The other three were 2 males and 1 female with an average age of 33. In these cases, the posterior descending branch bifurcated from the left hepatic duct, and stones were lodged in the dilated bile ducts distal to the junction of the left hepatic duct and the posterior descending branch. It is our conclusion that at least the former two were cases of “primary cholesterol hepatolithiasis” in view of the shape of the stones conforming to the hepatic duct, their easy morcellation, and the high cholesterol contents.

Prophylaxis of uric acid stone in patients with inflammatory bowel disease following extensive colonic resection

SummarySeven patients (13.0%) among 54 patients with inflammatory bowel disease treated by extensive colonic resection were complicated by renal stone. The mean urinary pH value in cases complicated by renal stones (5.3±0.4) was significantly lower than among those without stones (6.1±0.3, P<0.01). Sodium bicarbonate (4 gm/day, q.i.d.), was given to 11 patients with renal stones and/or hematuria, whose urinary pH was lower than 5.0, or whose urinary sediments were positive for uric acid crystals since Oct. 1985. Their urinary pH and Na concentration increased significantly and no renal stone complication has been seen in the treated group.

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile

SummaryA study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6±0.6 mg/ml, mean±SD, n=10), calcium bilirubinate gallstone bile (4.2±1.1 mg/ml, n=10), black pigment gallstone bile (1.9±0.6 mg/ml, n=4) and control gallbladder bile (2.3±0.5 mg/ml, n=9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of contorls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.

Epidermal growth factor inhibits cysteamine-induced duodenal ulcers in rats.

We examined the pathogenesis of cysteamine-induced duodenal ulcers in rats, especially with reference to epidermal growth factor (EGF). Control, cysteamine (400 mg/kg, s.c.), cysteamine + EGF (20 micrograms/kg/day, i.p.) submandibular resection (SMR), SMR + cysteamine, and SMR + cysteamine + EGF groups were examined for duodenal ulceration. With submandibular resectioning, endogenous EGF decreased, and with the administration of EGF (i.p.), endogenous EGF increased. In the SMR + cysteamine group, serum gastrin increased and the intragastric pH decreased remarkably compared to in the normal control group. The administration of exogenous EGF suppressed this change. Mucosal blood flow, the potential difference and hexosamine, as defensive factors, decreased markedly in the SMR + cysteamine group, but the administration of exogenous EGF reversed these changes. These results suggested that a decrease in EGF is involved in the pathogenesis of cysteamine-induced duodenal ulcers in rats.

Short chain fatty acid in intestinal obstruction

Short chain fatty acid (SCFA) and enteric bacteria in enteric fluid of 26 patients with non-strangulated intestinal obstruction were investigated. Sixteen to 905 mg/L of SCFA was detected in all the samples and acetic, propionic and lactic acid were prominent in the fraction. Concentration of SCFA reached a peak around the time of operation and then gradually decreased, in most cases. It also gradually decreased with clinical improvement in conservatively treated cases. Cultures of these enteric samples revealed 104–11/ml of SCFA producing bacteria. SCFA may be one factor related to inhibition of water and electrolytes absorption and lead to distention of the bowel.