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Endoscopic mucosal resection (EMR) enables one to examine resected specimens histologically and judge the curability by the histological findings. A mucosa and a part of submucosa can be resected by EMR. Therefore, mucosal cancers are indications for EMR. The present study showed that better indications for EMR were as follows: lesions less than 10 mm in size, lesions without ulceration, and lesions in the antrum or at the greater curvature. However, it is difficult to judge correctly before EMR whether the lesions are completely resected or not. The lesions with better indications are not always resected completely, and, conversely, the lesions more than 11 mm in size are completely resected at times. Therefore, it is most important to know how to deal with resected specimens. Specimens must be dealt with in strict conformity with the regulations. At present, when EMR may be regarded as the least invasive modality of curative sugeries, a new systematic treatment combining surgical laparotomic treatment and EMR is desirable for curative treatment of early gastric cancer.

Routine films of 596 upper GI endoscopies with the diagnosis of duodenitis were reviewed and a classification was made into granular (G), multi-polypoid (MP), reddened (R) and erosive (E) types. Two hundred and thirty-four histological specimens from 117 of the patients, as well as 100 specimens from 50 controls, were analyzed for villous obliteration, Brunner's gland dilatation and mucus depletion, erosion, mucosal hemorrhage and edema, atypia of the surface epithelium and gastric surface epithelial metaplasia. Inflammatory cell counts for polymorphonuclear and mononuclear cells in the epithelium, in the lamina propria together with a histological score was also made. On the basis of this study and a review of classifications of duodenitis in the literature, it is concluded that some endoscopical features like erosions and redness may represent more acute phases of duodenitis, mucosal elevations representing more hyperplastic changes and that the endoscopic classification into G, MP, R and E types seem relevant to use in clinical practice.

The detailed substrate specificity of the UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase to form the Sd(a+) blood group active carbohydrate determinant GalNAc beta 1-4(NeuAc alpha 2-3)Gal was studied using a membrane fraction prepared from human gastric fundic mucosa. Various sialosylated oligosaccharides and gangliosides were examined as acceptor substrates. Oligosaccharide substrates were fluorescence-labelled with 2-aminopyridine, and the transferase activity was quantified by h.p.l.c. using a reversed-phase column. The structures of the products were determined by glycosidase degradation and proton n.m.r. 3′-Sialyl-lactose (II3NeuAcLac), 3′-sialyl-lactotetraose (IV3NeuAcLc4), and 3′-sialyl-lactoneotetraose (IV3NeuAcnLc4) were good substrates for the beta 1-4GalNAc transferase in gastric fundic mucosa, but 6′-sialyl-lactoneotetraose (IV6NeuAcnLc4) or 6′-sialyl-lactose (II6NeuAcLac) were not. Gangliosides with a terminal NeuAc alpha 2-3Gal residue such as GM3, sialylparagloboside, GM1b and GD1a were also studied. The activity of beta 1-4GalNAc transfer to sialylparagloboside was much higher than that to GM2, GM1b or GD1a in spite of them having the same terminal residue. Measurement of the activity of the beta 1-4GalNAc transferase in biopsy specimens demonstrated that the activity was localized in gastric fundic mucosa and was absent in pyloric mucosa, intestinal metaplasia and gastric cancer tissue. Thus the beta 1-4GalNAc transferase present specifically in fundic mucosa required a NeuAc alpha 2-3Gal residue connected to either type-1-chain or type-2-chain oligosaccharides. In glycolipids, the acceptor specificity was restricted to NeuAc alpha 2-3Gal beta 1-4GlcNAc because the NeuAc alpha 2-3Gal beta 1-3GalNAc structure in ganglio-series glycolipids was not a good acceptor substrate.

Immunological determination of fecal hemoglobin and transferrin levels was performed in inpatients on an unrestricted diet, including patients with colon cancer or polyps and a control group. When hemoglobin levels of 5.1 micrograms/g feces and transferrin levels of 0.4 microgram/g feces were designated as positive, 48 of the 60 fecal specimens from colon cancer patients were positive. This result was significantly superior to that for another fecal occult blood immunological test (FECA-EIA) (p less than 0.005), and similar to the results of two chemical tests (guaiac and Hemoccult). Twenty-eight of the 78 fecal specimens from patients with colonic polyps were positive, again a result superior to the FECA-EIA (p less than 0.005) and similar to the chemical tests. Three of the 99 control fecal specimens were positive, which was a similar result to that obtained with the FECA-EIA and significantly superior to the chemical tests (both p less than 0.005). Thus, combined detection of fecal hemoglobin and transferrin levels can be used as a fecal occult blood test in patients without dietary restriction.

Endoscopic injection sclerotherapy (EIS) with ethanolamine oleate was performed in patients with esophageal varices either with (18 patients) or without (19 patients) pretreatment with haptoglobin. The serum levels of urea nitrogen, creatinine, and beta 2-microglobulin, the creatinine clearance, and the urinary levels of N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured before and after EIS. Indices of the glomerular filtration rate (serum levels of urea nitrogen, creatinine, beta 2-microglobulin; creatinine clearance) showed no significant changes after EIS in either the haptoglobin-treated or untreated groups. However, the increase in the urinary parameters after EIS (which are indices of renal tubular function) was suppressed in the haptoglobin-treated group (p less than 0.005 for urinary beta 2-microglobulin). Our results indicated that the administration of haptoglobin has a prophylactic effect on renal tubular dysfunction associated with the use of ethanolamine oleate in EIS.

Endoscopic therapy has been aggressively used for radical treatment of early gastric cancer, because endoscopic resection allows us to collect the removed tissue and to determine histopathologically whether the cancer lesion has been completely resected. In order to succeed in radical treatment, the complete resection of lesion and no lymph node metastasis are necessary. On the basis of thorough histopathological investigations into operated cases with early gastric cancer, the types of early gastric cancer which have no lymph node metastasis are considered to be as follows: 1) Intramucosal carcinoma type I type II a, measuring 30 mm or less type II b type II c, measuring 10 mm or less 2) carcinoma invading up to submucosal layer type II a + II c, measuring 10 mm or less type II a, measuring 20 mm or less type II b type II c, measuring 10 mm or less type II a + II c, measuring 10 mm or less However, indications of endoscopic resection should be more strictly decided due to diagnostic and technical problems. Eventually, it will be important to detect and resect intramucosal gastric carcinoma as small as possible in order that the lesion be completely resected. The success of curative treatment is evaluated by not only histopathological examination of resected tissue, but also through follow-up study. Therefore, various problems remain to be resolved in this treatment. A larger case sampling will serve to confirm the reliability of this form of therapy for early gastric cancer.

The natural killer (NK) activity and NK cell subsets in peripheral blood were evaluated in patients with inflammatory bowel disease (IBD), by using 51Cr release cytotoxicity assay and two color flowcytometry analysis. The peripheral blood NK activity was significantly lower in IBD than that in normal controls. This decrease of the NK activity was independent on the disease activity of IBD but dependent on the steroid medication. The total population of NK cells (Leu 7+ or 11c+ cells) did not change in IBD as compared with those of normal controls. However, the proportions of Leu7+11c- cells and Leu7-11c+ cells in IBD were higher and lower, respectively as compared with those of normal controls. These findings suggest that the maturation step of NK cell lineages might be impaired in IBD. The decrease of NK activity in IBD was supported by the change in the proportion of NK cell subsets described above. It was thought that such a change in NK cell subsets might be a specific finding in IBD patients, because it was not observed in patients with non-IBD colitis.

EAP therapy has been performed on 50 cases of advanced gastric cancer from January 1988 to September 1989. Adriamycin 20 mg/m2, Cisplatin 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. Complete success, PR, NC and PD were obtained in 48, 21, 20 and 7 cases, respectively, the rate of effectiveness being 43.8% with a confidence interval 95% of 30-58%. The rate of effectiveness by lesions for evaluation was high (30.4, 100, and 50% for primary lesion, Virchow's lymphnodal metastasis and liver metastasis, respectively). MST was 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus, it is thought that good control of leukopenia, a dose limiting factor remains to be examined.

To study the mechanism of self-protection of the gastric surface epithelium, we measured the pH gradient of the mucus gel layer in the isolated bullfrog antral mucosa with pH-sensitive microelectrodes in the Ussing chamber preparation. Under the control condition of 15mM HCO3- and 1.5% CO2 serosal perfusion, the pH on the interface between luminal solution and mucus gel layer (pHLMI) was 6.04 +/- 0.12 (n = 7), and the pH on the interface between the mucus gel layer and epithelial cell (pHMEI) was 5.69 +/- 0.13 (n = 7). When gastric acid secretion was stimulated by histamine (10(-4) M), the pHLMI became 5.43 +/- 0.12 (n = 4) and the pHMEI 4.40 +/- 0.18 (n = 4). Inhibition of acid secretion by cimetidine (10(-4) M) raised the pHLMI to 6.51 +/- 0.07 (n = 7) and the pHMEI to 6.23 +/- 0.08 (n = 7). Omeprazole (10(-4) M) also raised the pHLMI and the pHMEI to 6.78 +/- 0.13 (n = 7) and 6.56 +/- 0.13 (n = 7), respectively. These data suggested that the H+ ions secreted from the oxyntic cells were able to diffuse to the lateral side within the mucus gel layer, affecting the local pH just above the surface epithelial cells. Under high serosal HCO3- condition (45mM HCO3- and 1.5% CO2 in serosal side), the pHLMI and the pHMEI were elevated to 7.22 +/- 0.10 (n = 7) and 6.92 +/- 0.10 (n = 7), respectively. This result suggested that HCO3- secretion, which was served to neutralize the invading acid, depended upon the supply of HCO3- from the serosal medium. Thus, the serosal HCO3- would be working not only in the acid-protection, but also in the maintenance of pH gradient across the mucus gel layer.

The effect of haptoglobin (Hp) used on endoscopic injection sclerotherapy (EIS) was evaluated by examining the increase of serum free hemoglobin (FHb) and the changes of renal function. In control group, the increase of serum FHb (delta FHb) was paralleled with the volume of 5% ethanolamine Oleate (EO) injected intravariceally, and free Hp (FHp) was disappered in this group soon after EIS. On the contrary, in the group treated with Hp, neither the increase of FHb nor decrease of FHp were recognized. The significant increase of urine beta 2 microglobulin and NAG was recognized in control group. Therefore, if Hp is used at initial EIS, it would be prevented that serum FHb due to intravascular hemolysis increases, consequently the possibility of renal dysfunction.

We had clinicopathologically studied early cancer-like advanced gastric cancer in relation to peptic ulcer (UI). Early cancer-like advanced cancers with the difficulty to distinguish from early gastric cancer were selected for materials. Result were as followed: 1) Early cancer-like advanced cancers were consisted of 133 lesions, of which 128 lesions (96.2%) had peptic ulcer in cancerous lesion (73 lesions were active stage and 55 lesions were scarring stage). 2) Early cancer-like advanced cancers were 17.0% in all advanced gastric cancers. Proper muscle cancer (in which depth of cancerous invasion is up to proper muscle coat) was more common in early cancer-like advanced cancers than in Borrmann type advanced cancers. 3) Early cancer-like advanced cancers with peptic ulcer showed wide intramucosal cancerous infiltration. Thus, average of maximum diameter was 51.8 mm. 4) Those ulcer were commonly reaching to proper muscle coat or subserosa. Submucosal fibrosis was prominent and scattered proliferation of tumor cells were often seen within fibrosis. 5) Extent of cancerous infiltration in mucosa was more wide than that in submucosa. The above findings have led us to consider that early cancer-like advanced cancers have grown because of high degree submucosal fibrosis by the deep ulcerations due to "malignant cycle".

We treated a 40-yr-old Japanese woman who had Churg-Strauss syndrome (CSS), as diagnosed by characteristic clinical features and histological findings; in addition, peculiar multiple colonic ulcers were seen during the course of her illness. Although gastrointestinal symptoms are often seen in CSS, there are few descriptions of lesions in the gastrointestinal tract. In the English literature, the gastrointestinal manifestations of CSS include eosinophilic gastroenteritis, but the mucosa is not usually ulcerated. On the other hand, Japanese cases are characterized by multiple ulcers which are considered to be caused by ischemia secondary to the vasculitis. Most of the reported cases have not been diagnosed until laparotomy or autopsy, and our case is the first with multiple ulcers throughout the entire colon as a complication of CSS.

A double blind, multicenter, six-month maintenance study was performed to assess the efficacy and safety of sucralfate (S), cimetidine (C), and their combination (S + C) in the prevention of peptic ulcer recurrence in a six-month observation period. 127 patients with gastric ulcer (GU) (group S: 39, group S + C: 48, group C:40) and 103 patients with duodenal ulcer (DU) (group S: 35, group S + C: 36, group C:32) were available for statistical analysis. Six to 12 months after healing of GU, the cumulative recurrence prevention rates by Kaplan-Meier method were 89.7----80.3% in group S, 97.6----72.6% in group S + C, 84.5----44.6% in group C. In duodenal ulcer they were 75.9----41.9% in group S, 87.8----47.7% in group S + C, 80.8----40.5% in group C. These results indicate that maintenance therapies of S and S + C are effective and safe for the prevention of gastric ulcer recurrence.

The expression of LeY (Fuc alpha 1----2Gal beta 1----4 [Fuc alpha 1----3]GlcNAc beta 1----R) (in which Fuc is fucose, Gal is galactose, and GlcNAc is N-acetylglucosamine) defined by monoclonal antibody AH6 in various locations of human colonic epithelia, colonic polyps, and adenocarcinomas has been studied. In normal colonic mucosa, strong staining by AH6 was observed in the proximal regions such as the terminal ileum and cecum. The staining was, however, greatly reduced in the epithelia of the ascending colon and became very weak in the epithelia of transverse, descending, and sigmoidal colon as well as the rectum. Of 481 crypts in 40 biopsy samples of the epithelia of normal sigmoidal colon, 421 crypts did not show any staining, and only a weak staining of the lowest crypt area was observed in 60 crypts (12%); of 474 crypts in 40 biopsy samples of normal rectal epithelia, 110 crypts (26%) showed a weak staining. At the fetal stage, the LeY staining was much more intense in all locations of the colon than in corresponding locations of adult epithelia, and staining was observed in the epithelia of the sigmoidal colon and rectum. A strong staining was observed in 24 of 25 cases of colorectal adenocarcinomas, irrespective of their original location. The expression of LeY in polyps was correlated with histological type as well as the degree of dysplasia of the polyps. Of various adenomas examined, tubular adenomas, many of which showed mild or moderate dysplasia and less malignant potentials, displayed the least LeY expression. Tubulovillous and villous adenomas, which have higher malignant potential and showed a higher incidence of severe dysplasia, showed a greater area and intensity of LeY expression. No LeY was detectable in juvenile polyps, and only a very weak staining was observed in the dysplastic area of hyperplastic polyps. The extent and intensity of staining in various adenocarcinomas and adenomas could not be correlated with blood group ABO status of the hosts nor with location of the tumors. These results suggest that LeY in colonic adenocarcinomas and polyps at the distal region of the colon and rectum is a typical oncofetal antigen and is a useful marker for diagnosis of colonic cancer. Its expression in colonic polyps can be correlated with the degree of dysplasia and may indicate the degree of malignant potential of the polyp. Thus, LeY expression in polyps may have prognostic value.

In the present study plasma fibronectin levels were determined in patients with hematopoietic malignancy, particularly leukemias, in an effort to clarify their clinical implications. Among leukemia patients, those with AML, ALL, ATL or CLL had various plasma fibronectin levels that were higher in some cases, while lower in others, as compared to normal control values. An elevation of the fibronectin level was noted often in APL, while lower fibronectin values were observed in many instances of CML. In these types of leukemia, acute exacerbation as well as supervention of infection tended to be associated with lower than normal levels of fibronectin. An especially marked depression of fibronectin occurred, when leukemia was complicated by sepsis or DIC, in which a good parallel was noted between the progress of disease and the fibronectin level. In lymphoproliferative diseases, the fibronectin value varied widely, but low fibronectin levels were frequently associated with intercurrent infection or an extreme deterioration of the general physical conditions.

Ultramicro-pH electrodes were used to determine intracellular pH changes induced by luminal perfusion of acid and alcohol in the gastric mucosa. In preparations of the bullfrog antral mucosa mounted on a horizontal type Ussing chamber, we determined intracellular pH (pHi) in situ of the surface epithelial cells exposed to HCl in the presence or absence of 10% ethanol in the luminal side. The pHi and apical membrane potential (LEM) of the surface epithelial cells were measured with double-barreled liquid ion-exchanger pH microelectrodes. In normal control conditions, the mucosal pHi was 7.43 +/- 0.01 and LEM was 29.5 +/- 0.7 mV (SE, n = 54). Acidification of luminal perfusate to pH 3.5 had no influence on pHi. Exposure to luminal 1 mM HCl (luminal pH: pHL = 3.1) lowered pHi to 7.31 +/- 0.01 (n = 6). Addition of 10% ethanol (EtOH) to luminal perfusate at pH 4.2 (0.1 mM HCl) led to immediate and progressive acidification of pHi (delta pHi = 0.12 +/- 0.02, n = 6). Hyperpolarization of LEM (by several mV) was also observed under such conditions, indicating an altered ion permeability of the apical membrane. These results suggest that even a low concentration of alcohol added to the gastric lumen causes a significant change in the surface epithelial cells, and this change becomes manifest when the luminal fluid is acidified to pH lower than 4.

Immunosuppressive acidic protein (IAP) is among the immunosuppressive factors so far detected in the blood of cancer patients. This study was undertaken to determine the blood level of IAP in patients with carcinoma of the gastrointestinal tract, particularly the stomach, and to define the clinical implications of IAP for the therapy. A close correlationship was established between the serum IAP level and the gross degree of malignancy of the tumor and clinical stage of disease, notably in patients with gastric cancer; the serum IAP level was increased with as the disease advanced, the increase being significant in the presence of metastasis or extensive spread of the lesion.