Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas.

Tissues of normal human gastric mucosae and 15 advanced gastric carcinomas were studied immunohistologically for the presence of receptors for epidermal growth factor (EGF) by use of a murine monoclonal antibody (528IgG), which reacts with the binding domain of human EGF receptor. On normal gastric mucosae, only parietal cells showed positive staining. On cancer tissues, definite staining was observed in 9 of 15 cases. Their staining intensities were variable and weaker in general compared to those of either gastric parietal cells or normal tonsilar squamous epithelium. No apparent correlation of EGF receptor staining with the grade of histologic differentiation or lymph node metastases of these gastric carcinomas was noted.

Expression and function of class II antigens on gastric carcinoma cells and gastric epithelia: differential expression of DR, DQ, and DP antigens.

The expression of human histocompatibility leukocyte antigen class II antigens on gastric epithelia and gastric carcinoma (GaCa) was studied with the use of murine monoclonal antibodies to DR, DQ, and DP antigens. DR and DP antigens but not DQ antigens were demonstrated in fundic glands of normal gastric epithelia, and DP+ cells were located in part of the DR+ epithelia. Of 15 GaCas examined, 11 expressed DR antigen, and the degree of the expression varied considerably among the specimens. DP antigen was found in 3 of the 11 DR+ carcinomas, and the DQ antigen was found in one of the 3 DR+ DP+ specimens. Thus the expression of class II antigens in normal gastric epithelia and GaCas appears to be in the order of DR, DP, and DQ. Studies on 3 GaCa cell lines (Kato III, MKN28, and MKN45) demonstrated that 1 line (Kato III) expressed DR antigen only, and the remaining lines were negative. Interferon (IFN)-gamma treatment enhanced the expression of DR antigen on Kato III cells and induced expression of DQ and DP antigens. The IFN-gamma treatment also induced expression of DR antigen but not DQ or DP antigens in 1 of the 2 negative cell lines. The induction of the class II antigens by IFN-gamma was shown to be dose dependent. However, maximal induction of DQ and DP antigens on the Kato III cells and DR antigens on MKN45 cells required 10 times more IFN-gamma than that needed for the maximal expression of DR antigen on Kato III. Northern blot analyses of cytoplasmic RNA from these cells were in agreement with and affirmed the above-described expression of the class II antigens on the cell lines. The DR antigen on the Kato III cells was capable of stimulating allogeneic lymphocytes in MLR, and its stimulatory activity was significantly enhanced by IFN-gamma. These results demonstrated a differential expression of class II antigens in the "DR, DP, and DQ order" in normal gastric epithelia, GaCa cells, and GaCa cell lines, suggesting different mechanisms acting discordantly on the expression of each of these antigens and that the DR antigen on the GaCa cell lines possesses MLR-stimulatory ability.

Enhancing effect of bile and bile acid on stomach tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The carcinogenic or cocarcinogenic effects of bile or bile acid on stomach carcinogenesis were investigated in inbred W rats. Bile or bile acid was introduced into the stomach by choledochogastrostomy or with food after the administration of N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] in drinking water. The animals that received MNNG and bile or sodium taurocholate (CAS: 145-42-6; N-choloyltaurine sodium salt) had a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the relevant MNNG-treated controls. The result suggested an enhancing effect of bile and sodium taurocholate in stomach tumorigenesis.

Establishment of a cell culture line from a transplantable rat stomach cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine.

A cell line designated as BV9 was established in culture from a transplantable rat stomach cancer, which was originally induced in the glandular stomach of a Wistar rat by p.o. administration of N-methyl-N'-nitro-N-nitrosoguanidine. The monolayer cells, which have been subcultured for more than 35 passages, revealed pleomorphic features. Chromosomal analysis showed hypertetraploidy (mode, 95), and marker chromosomes were present. Cultured cells were injected s.c. into cyclophosphamide-conditioned syngeneic rats and produced tubular adenocarcinomas resembling the original tumor.

Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases.

We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.

Results of 90 consecutive hepatectomies for hepatocellular carcinoma: a multivariate analysis of survival.

The surgical results and postoperative management of 90 patients with hepatocellular carcinoma (HCC) who underwent hepatectomy were reviewed, and clinical factors relating to HCC were analyzed to determine what type of HCC responds best to hepatectomy. The patients consisted of 69 men and 21 women. Serum anti-hepatitis C virus was positive in 76.9% of patients and hepatitis B surface antigen was positive in 18.9%. The operative procedures consisted of right lobectomy in six patients, left lobectomy in seven, right hepatic segmentectomy in eight, left lateral segmentectomy in 13, two adjoining subsegmentectomy in 17, subsegmentectomy in 29, and partial hepatectomy in 10. Liver cirrhosis was confirmed histopathologically in 63 patients. There were two operative deaths and two other in-hospital deaths. During the follow-up period, HCC recurred in 64 of the remaining 86 patients at the following sites: liver in 56 patients (87.5%), bones in four (6.3%), lymph nodes in three (4.7%), and lung in one (1.6%). Transcatheter arterial chemoembolization was performed in 22 of the patients with recurrence, transcatheter arterial chemoembolization in combination with percutaneous ethanol injection was performed in 14, hepatectomy was performed in six, and irradiation with Linac x-rays was performed in eight. The cumulative 3- and 5-year survival rates were 63.8% and 37.8%, respectively. Univariate and multivariate analyses of factors influencing survival disclosed that having a single HCC nodule of up to a maximal diameter of 4.0 cm, an absence of intrahepatic metastasis, and a functional liver reserve estimated as clinical stage I contributed significantly and independently to increasing the survival rate.

Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis.

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2-12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2-3 or 4-5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.

[A case of superficial carcinoma of the esophagus on esophageal varices]. / Un cas de carcinome superficiel de l'oesophage sur varices oesophagiennes.

We report a case of superficial esophageal carcinoma in a patient with esophageal varices. Esophagogram revealed a 2 cm large irregular mucosal elevation during work-up for esophageal varices which was acertained on endoscopical examination to be carcinoma. Biopsy material showed moderately differentiated squamous cell carcinoma. Subtotal esophagectomy was performed followed by reconstruction by cervical esophagogastrostomy through the retrosternal route. Few resected cases of esophageal carcinomas accompanied by esophageal varices have been reported because 1) early radiographic abnormalities of small superficial esophageal carcinomas can be overlooked in the case of large varices and 2) the number of operable cases is limited because of associated liver cirrhosis.

[Successful resection of mediastinal and abdominal recurrent tumors of esophageal leiomyosarcoma 12 years after surgery].

A 57-year-old woman admitted to our hospital in October, 1988 because of the tumor of the abdominal wall and abnormal shadows of right chest wall and right upper mediastinum. Her esophagus had been resected and reconstructed by the stomach roll because of the esophageal leiomyosarcoma in May, 1976. Clinical examinations revealed that the abdominal mass and chest shadows were the recurrence of the leiomyosarcoma. The abdominal tumor was resected on 17th October, 1988. On 14th December, 1988 right thoracotomy was performed. Chest wall tumor (40 x 30 x 20 mm) and mediastinal tumor (45 x 40 x 35 mm) were resected completely. The mediastinal tumor was adhered to the remnant esophageal muscle layer. Microscopic section of the tumor showed spindle cell sarcoma with fine calcification, and it was diagnosed as the metastatic leiomyosarcoma.

[International perspectives on the treatment of gastric cancer].

Our experience of treatment of gastric cancer in European and developing countries suggested the necessity of the establishment of both operative and chemotherapeutic modalities. These modalities should be first based on theoretically convincing data and secondarily well analyzed from the viewpoint of cost-effectiveness.

[A case of advanced gastric cancer successfully treated with combination chemotherapy using THP, 5'-DFUR and CDDP, followed by surgical resection].

We reported a patient with advanced gastric cancer and a liver metastasis, who responded remarkably to combination chemotherapy using THP, 5'-DFUR and CDDP. The patient was administered four courses of THP (15 mg/m2/day, on day 1, iv), 5'-DFUR (1400 mg/m2/day, on days 1-4 and 15-18, orally), and CDDP (80 mg/m2/day, on day 5, iv) every 4 weeks. As a result, both the primary and metastatic tumors decreased remarkably in size at more than 19 weeks (PR) and we performed curative total resection of the stomach and partial resection of the liver. Histologically, the effects of chemotherapy on gastric focus were evaluated as grade 1a and the liver metastasis completely disappeared. This combination therapy proved useful to treat advanced gastric cancer in this patient.

[Leiomyoma and leiomyosarcoma of the esophagus: report of 9 cases and review of the Japanese literature].

Seven cases of leiomyoma and two cases of leiomyosarcoma of the esophagus were presented. Review of the Japanese literature revealed a total of 260 cases of the former and only 35 cases of the latter, including our own cases. They occurred more frequently in males than females, by a ratio of 1.6:1 and 1.8:1, respectively. The patients with leiomyosarcoma distributed in higher age groups. The most frequent symptom was dysphagia in both groups of the cases, but in cases of leiomyosarcoma the incidence was much higher and the duration of the symptom was shorter. About 20% of the patients with leiomyoma were asymptomatic. Although the size of leiomyosarcoma tended to be larger, giant leiomyomas more than 10 cm in diameter were found in 18% of the cases. The lower third of the esophagus was the site of both tumors in over half of the cases, the middle third being the next frequent. The surgical removal by enucleation was the procedure of choice for leiomyoma. However, when either the tumor is densely adherent to the mucosa for considerable length or accidental extensive mucosal tear occurs, esophageal resection is recommended. Postoperative morbidity was minimal and results were generally excellent. On the contrary, esophageal resection including the tumor was indicated for leiomyosarcoma. The long-term results were poor particularly in cases of infiltrating-type lesions, though survival data could not be fully evaluated.