Verapamil enhancement of antitumor effect of cis-diamminedichloroplatinum(II) in nude mouse-grown human neuroblastoma.

The antitumor effect of combined use of cis-diamminedichloroplatinum(II) (CDDP) and verapamil, a calcium influx blocker, was examined in neuroblastoma transplanted to BALB/c athymic mice. The response of the tumor to CDDP was related to the dose administered. Regression of the tumor was observed when CDDP was administered at 4.2 mg/kg/injection. The retardation of tumor growth was observed in the group to which CDDP was administered at 2.1 mg/kg/injection. When verapamil was administered with CDDP, regression of the tumor was observed in the group treated with CDDP at 2.1 mg/kg/injection, and the retardation of tumor growth was observed in the group treated with CDDP at 1.4 mg/kg/injection. These results indicate that verapamil enhances the antitumor effect of CDDP against transplanted neuroblastoma in BALB/c athymic mice.

Selective elevation of the N1-acetylspermidine level in human colorectal adenocarcinomas.

The association of N1-acetylspermidine with human colorectal adenocarcinomas has been evaluated in this study. Free polyamines and their monoacetylated forms in adenocarcinomas, adenomas, and apparently healthy mucosae were determined using high-performance ion-exchange chromatography. The N1-acetylspermidine levels in well- and moderately differentiated adenocarcinomas were 27.30 +/- 3.13 (S.E.) (n = 99) and 22.86 +/- 3.60 (n = 22) nmol/g, wet weight, respectively. These values were significantly higher than those of benign adenomas (5.38 +/- 0.85 nmol/g, n = 31) and of control mucosae. The N1-acetylspermidine levels in control mucosae on the oral and anal side of adenocarcinomas were 5.84 +/- 1.44 (n = 57) and 7.92 +/- 2.89 (n = 50) nmol/g, respectively; no significant difference was observed between control mucosae and adenomas. The mean levels of three polyamines, putrescine, spermidine, and spermine in both adenomas and adenocarcinomas were about twice as high as those of control mucosae. The molar ratios of spermidine to spermine were significantly greater in both adenomas and adenocarcinomas than in control tissues. There was no obvious correlation between the free polyamine concentrations and the degree of malignancy of the colorectal tumors. These results suggest that the metabolism of N1-acetylspermidine in colorectal adenocarcinomas is quite different from that in adenomas and in nonneoplastic mucosae and that N1-acetylspermidine can be a promising biochemical marker of cancer in the human large intestine.

Histopathological classification and malignant change in gastric polyps.

A total of 611 gastric polyps from 275 cases were studied and were classified into four subtypes. Type I was the most common type and types II, III, and IV were less common. Type I and II, considered to be non-neoplastic polyps because of the absence of dysplasia, showed an extremely low malignant potential. Type III showed a two layer structure, the upper layer of which was composed of dysplastic epithelia. This type showed a low malignant potential despite the dysplasia. The type IV polyp showed macroscopical and histological findings similar to those of colonic adenoma. This type was considered to be truly neoplastic and to be the most important of the four subtypes because of its high malignant potential. Type III and IV should be clearly separated and treated differently.

Adenomatosis of small intestine: case report.

A patient complained of severe diarrhoea for about four years. About 2.5 m of the jejunum was resected and duodenal polyps were also removed at laparotomy. Histologically, they were tubular or tubulovillus adenomas, which closely resembled colonic adenomas. No malignant change was detected in these adenomas. Severe inflammatory changes were seen in the jejunal mucosa and various gut hormones were seen in the same area. As far as we know no similar case with adenomatosis of the small intestine has been reported. We were unable to establish any association between adenomas and severe watery diarrhoea.

Histopathogenesis of intestinal metaplasia: minute lesions of intestinal metaplasia in ulcerated stomachs.

Minute lesions of intestinal metaplasia composed of a few metaplastic tubules were observed in the gastric mucosa during routine histological examination of gastrectomy specimens. The histological findings indicated that these lesions might be an initial stage of more advanced intestinal metaplasia. Accordingly, more than 18,000 serial sections in 10 stomachs with chronic ulcers were examined to clarify the histopathogenesis of the intestinal metaplasia. It was concluded from the three dimensional reconstruction of minute intestinal metaplasia lesions that these lesions originated during the regenerative process of healing of gastric erosions. The lesions were roughly globoid with a depression on the surface. It is thought that with continuous formation and healing of gastric erosions, more extensive intestinal metaplasia lesions would be formed by an increase in size and confluence of these focal minute intestinal metaplasia lesions.

Ultrastructural study of two subtypes of gastric adenoma.

An ultrastructural study was performed to identify any differences in fine detail between type III and IV gastric polyps, which seem to differ from each other because they have different histological features and malignant potential. Clear ultrastructural differences were found, implicating microvilli, mucous granules, interdigitations, ribosomes, mitochondria and nuclei. Although these two subtypes have often been grouped together as borderline lesions or adenomas, the findings imply that they should be treated as essentially different.

[Concentrations of cefmenoxime and cefotiam in the bile and gallbladder tissue following intravenous administration in patients with biliary tract diseases].

To test the effectiveness of cefmenoxime (CMX) and cefotiam (CTM) in patients with biliary tract diseases, concentrations of either antibiotic were measured after an intravenous bolus injection of 1.0 g of CMX or CTM, or simultaneous injection of both (1.0 g each). CMX or CTM was injected in 76 patients with biliary tract diseases (mostly cholelithiasis) prior to a cholecystectomy and concentrations of CMX or CTM were measured by the bioassay (agar well) method at 30 to 60 minutes after the injection. Average concentrations of both CMX and CTM in gallbladder bile and gallbladder tissue sufficiently exceeded the minimal inhibitory concentration (MIC) against main causative organisms of biliary tract infections. Concentrations of both antibiotics in gallbladder bile were significantly higher in patients with patent cystic ducts than with obstructed cystic ducts. Concentrations of both antibiotics in the gallbladder tissue reached at a similar high level regardless of the patency of the cystic ducts, but concentrations were lower in severely inflamed gallbladders. CMX and CTM were administered alternatively (cross-over fashion), or simultaneously (combined) to 13 patients with T-tube drainage or percutaneous transhepatic cholangio-drainage, and concentrations of both antibiotics in bile from the drainage tube were measured by high performance liquid chromatography at hourly intervals after the injection. Concentrations of both antibiotics were far greater than MICs against main attributable microorganisms in biliary tract infections. The concentration of CMX slightly exceeded that of CTM. Concentrations of both antibiotics were lower in bile of patients showing abnormally high serum GTP, A1-P, and total bilirubin levels than in bile of patients with normal values of these variables. It is speculated that the secretion of both antibiotics in the bile may decrease in cases with severe hepatic failure, but effective concentrations of both antibiotics in the gallbladder tissue should be maintained as long as the blood circulation in the gallbladder was maintained.

[Experimental study on combination chemotherapy of UFT and calcium antagonist in gastric cancer].

The antitumor effect of combined use of UFT and verapamil, a calcium antagonist, was examined in gastric cancer transplanted to BALB/c athymic nude mice. Four experimental groups included Group I (Control) which was administered 3% Gummi Alabicum (p.o.), Group II (UFT) which was administered 64.8 mg/kg UFT (p.o.), Group III (UFT + verapamil) which was administered UFT and 10 mg/kg verapamil (s.c.) and Group IV (verapamil) which administered same doses of verapamil. All mice were sacrificed at the day of 12 and pathological and flow cytometric studies were performed to those tumors. At the day of 8, significant retardation of tumor growth was observed in Group II and Group III compared with Group I (P less than 0.05). The ratio of tumor retardation of Group III was more predominant than that of Group II at the day of 9 (p less than 0.05). However, no difference in pathological and flow cytometric changes was observed between Group II and Group III. Weight loss and death, as side effects, were found in Group II and III. It was assumed that this may be depend on the over dose of UFT or methods of administration. These results suggested that combination chemotherapy of UFT and verapamil was effective in the retardation of gastric cancer, however the doses of UFT and verapamil have to be reexamined in order to control the side effect.

[Clinical significance of a physical activity index based on calorimetry in the assessment of quality of life after total gastrectomy].

In order to characterize the objective diagnostic criteria concerning quality of life (QL) of patients after total gastrectomy, a physical activity index (PAI) or a concept of daily physical activity was developed. Sixty patients of gastric cancer, of whom 38 patients underwent long loop Roux-en-Y gastrojejunostomy (LLRY) procedure after total gastrectomy, 13 patients gastroduodenostomy (Billroth I) and 9 patients gastrojejunostomy (Billroth II) after subtotal gastrectomy, respectively, were evaluated as part of this study. In addition, 3 cases of pancreatoduodenectomy (PD) and 5 cases of total esophagectomy were also evaluated. The evaluation of QL was based upon a clinical assessment and administration of patient questionnaire. The assessment of the PAI was performed by measuring the individual's whole day energy expenditure based upon 24 hour heart rate ratio (24h-HRR) method and the basal metabolic energy expenditure. The daily physical activity was graded into four categories according to the PAI value; light, moderate, moderately heavy and heavy. The results obtained were as follows: The value of the energy expenditure predicted by 24h-HRR method and that based on the results of bicycle ergometry (VO2/HR method) showed close correlation. There was no significant difference in the whole day energy expenditure among four operative procedure groups (Billroth I, Billroth II, LLRY and total esophagectomy). More than 80 per cent of LLRY patients, whose QL was evaluated as "excellent" or "good", showed no less than "moderate" PAI. In addition, one of the four patients whose QL was "fair" was categorized into "light" and the remaining three were "moderate".(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term maintenance of human gall-bladder epithelia as xenografts following explant organ culture].

The purpose of present study is to establish a method that should enable us to keep a human gall-bladder epithelial tissue alive for a period long enough to observe morphological change after an exposure to a certain carcinogenic agents. Human gall-bladder epithelia obtained from surgically resected specimen were kept as an explant organ culture in vitro for the first 2 weeks. They were, then, xenotransplanted to the subcutaneous (S.C.) space of the athymic nude mice. The gall-bladder tissues obtained from 7 cases of cholecystolithiasis and 1 case of cholecysto-choledocholithiasis were used as materials in the present study. And the longest survivor among them in the nude mice was extensively studied in the present paper. After an interval of 4 to 27 weeks, the xenografts were recovered from the recipient mice and studied by light microscopy and histochemistry. The morphological changes of the explant epithelia during the organ culture were also studied. Parts of the explants were implanted in 6 nude mice. Each of the mice received 3 pieces of explants on the s.c. space in both of their flanks. All xenografts showed subcutaneous cyst formation. The cyst obtained 4 weeks after the implantation was consisted of a monolayer of cuboidal epithelial cells and those recovered from the recipient mice 24 and 27 weeks after the implantation were consisted of well growing columnar and cuboidal epithelial cells. In addition, sinus-like structures were observed beneath the cystic epithelia. The viability of the cells was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathological study of intestinal metaplasia of postmortem stomachs in the aged Japanese.

The incidence and extent of intestinal metaplasia of the stomach in aged Japanese has been studied. Histological studies were carried out on 422 stomachs, obtained at autopsy in Tokyo Geriatric Hospital from 1957 to 1969. The average age of the subjects in this series was 76 yr. Intestinal metaplasia was classified into six types according to its distribution: antral type 14.5%, intermediate zone type 1.7%, cardiac type 4.0%, cardiac and antral type 3.8%, diffuse type 62.8%, and nonmetaplastic type 13.3%. Diffuse type was found to gradually increase in incidence with increasing age and a correlation was found between the extent of the intestinal metaplasia and the degree of atrophic change of the gastric mucosa. Two spreading patterns of the intestinal metaplasia were also observed.

Adenoma of the rectum with multiple foci of signet-ring cell carcinoma. Report of a case.

A case with multiple foci of signet-ring cell carcinoma in an adenoma of the rectum is presented. Four foci of the signet-ring cell carcinoma and four foci of the common type of adenocarcinoma were found independently in a large polypoid tumor. An originating point of one of the signet-ring cell cancer foci was shown by an extensive serial sectioning study.

A pilot study on the usefulness of a new test for mass screening of colorectal cancer in Japan.

A new screening test (Shamsuddin and Elsayed, 1988) based on the enzymatic detection of the disaccharide beta-D-Gal(1----3)-D-GalNAc in the rectal mucus of patients with colorectal (CR) cancer and precancerous conditions such as inflammatory bowel disease (IBD) and polyp (precancerous lesions) was evaluated in 85 Japanese patients. Following a 15-minute reaction, a sensitivity of 80.0% (8/10) for CR cancer and 72.2% (8/11) for precancerous lesions was obtained. The overall specificity for combined CR cancers and precancerous lesions was 62.2% (28/45). Correlation with abnormal mucin production in the tissues of CR cancer and precancerous lesions was studied by high-iron diamine-Alcian blue and/or periodic acid-Schiff-Alcian blue (pH = 1.0). The agreement of the results with this test was 77.8% (7/9) for CR cancers and 75.0% (6/8) for precancerous conditions. Because of the simplicity of this test, low cost, stability of the sample and reagents and accuracy for CR cancer and precancerous lesions, the test may have potential use for mass screening of cancer and high risk individuals, particularly CR cancer in Japan.

Appraisal of surgical treatment for distal ulcerative colitis.

Most patients with ulcerative colitis respond well to medical treatment, however surgical treatment may be required in cases with severe clinical symptoms. We treated eight patients with distal ulcerative colitis (DUC), limited to the rectum and distal sigmoid colon, who were treated at St. Mark's Hospital by excision of the rectum and sigmoid colon with permanent colostomy. Four who did not respond to medical treatment and had severe and intermittent symptoms of long-standing, three with no control of the distressing diarrhea with a shorter history, and those with a severe dysplasia evidenced by rectal biopsy were surgically treated. Two of eight had a recurrence at the proximal colon within 6 and 10 years respectively but responded well to conservative management. From these observations it concluded that the procedure for patients with DUC may be one of adequate operations. Histological features of the resected specimens did not relate to the postoperative outcome of these patients.