Expression of blood group-related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), CA19-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach.

The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia.

Effects of SMS 201-995, a somatostatin analogue, on the exocrine pancreatic secretion and gut hormone release in dogs.

The effect of SMS 201-995, an analogue of somatostatin, on pancreatic exocrine secretion was investigated in both interdigestive and digestive states in dogs. In four dogs with gastric and Thomas duodenal cannulas, the pancreatic juice was collected by direct cannulation of the main pancreatic duct. SMS 201-995 was infused intravenously at doses of 0, 15, 30, 60, and 120 ng/kg/hr for 2 to 3 hours in the following experimental conditions: (1) interdigestive pancreatic secretion, (2) pancreatic secretion stimulated by the intravenous infusion of both secretin, 0.06 CU/kg/hr, and cholecystokinin octapeptide (CCK8), 0.03 microgram/kg/hr, and (3) pancreatic secretion after ingestion of a test meal. Pancreatic juice was analyzed for volume and outputs of bicarbonate and protein. Plasma levels of motilin, pancreatic polypeptide (PP), CCK, and secretin were determined by radioimmunoassay. SMS 201-995 inhibited significantly the pancreatic secretion and release of hormones, including secretin, CCK, PP, and motilin, in all three experimental conditions. The inhibitory action of SMS 201-995 on pancreatic secretion and hormone releases was dose dependent.

Clinicopathological analysis of synchronous multiple gastric carcinoma.

Clinicopathological analysis was performed on 839 cases surgically resected for gastric carcinoma. The incidence of multiple gastric carcinoma was 4.8% (40 cases, 97 lesions). Multiple carcinoma was more frequently observed in early than in advanced carcinoma (P less than 0.01). The rate of intestinal type lesions was significantly (P less than 0.01) higher in multiple than in single gastric carcinoma, and all of the intestinal type carcinoma correlated with intestinal metaplasia, which is assumed to be closely related to pyloric and atrophic fundic gland area. Eight cases (20.0%) of multiple carcinoma were both in the upper one-third and lower one-third of the stomach. Twenty-nine (51.9%) of the accessory lesions were not detected pre-operatively; 12 (21.1%) of them were detected only by postoperative histology. Twelve (48.0%) of 25 early cancerous foci located in the anterior wall and greater curvature were overlooked before operation. These results indicate that the whole stomach must be carefully examined to detect accessory carcinoma before gastric surgery, especially for intestinal type carcinoma, with greater attention paid to the anterior wall and greater curvature, and that complete removal of the pyloric and atrophic fundic gland area would be required for distal gastrectomy.

The effect of iron on experimental colorectal carcinogenesis.

The effect of parenteral and oral iron was examined in the rat 1,2 dimethylhydrazine (DMH) colorectal carcinogenesis model in a series of experiments. Parenteral supplementation of iron was found to augment tumor yield (p = 0.012) and oral iron was found to augment tumor incidence (p = 0.03, when control groups were combined). In addition, phytic acid, a significant component of dietary fiber was found to reverse the augmenting effect of oral iron on tumor yield and incidence (p = 0.09 for both). Furthermore, in a short term DMH nuclear toxicity assay, analysis of the karyorrhectic index (KI), there was no difference in the KI between oral iron and phytate dietary groups (p = 0.53 for the left colon and p = 0.2 for the right colon), implying that iron's effect on colorectal tumor induction takes place during the promotional phase of carcinogenesis and not during initiation. These experiments support the epidemiologic observation that dietary iron may augment colorectal cancer risk and that the mechanism by which dietary fiber diminishes colorectal cancer risk may be the chelation of dietary iron by the phytic acid component of dietary fiber.

The effect of dietary selenium deficiency on acute colorectal mucosal nucleotoxicity induced by several carcinogens in the rodent.

BACKGROUND: Selenium (SE) has been inversely associated with colon cancer risk. Two potential mechanisms of this effect were examined in a rodent short-term carcinogenesis assay: whether dietary SE deficiency altered the initiation aspect of carcinogenesis in the colon, and whether SE altered carcinogen metabolism. SETTING: Animal laboratory. SUBJECTS: 52 Sprague-Dawley rats, divided into a SE diet deficient group (0.002 parts per million; ppm) and a SE sufficient (0.2 ppm) group. ENDPOINTS: Weight, serum SE concentration, and karryorhectic index (KI), which is a measure of acute carcinogen induced nuclear toxicity in the colonic mucosa. METHODS: After three weeks of acclimation to the diets, eight animals from each dietary group were injected with one of the following: dimethylhydrazine (DMH), a colon specific carcinogen, its metabolite, methylazoxymethanol (MAM), or 0.9% sodium chloride. Twenty-four hours after injection the colons were removed, blood drawn, and the stained colons assayed for nuclear aberrations. RESULTS: No weight differences were generated by the dietary variations. Low-dietary SE resulted in serum SE declining markedly in the study period to 6 ng/ml versus 33 ng/ml in the SE sufficient group. Diet alone, and variations in weight gain, did not alter the KI. Both carcinogens greatly increased the KI in both the left and right colon. A SE-deficient diet was associated with a higher KI in both carcinogen groups in the right colon, with statistical significance for both the left and right colon in the MAM injection group. CONCLUSIONS: Dietary SE deficiency is associated with increased KI of the colon in MAM treated rats. SE, therefore, has a protective effect in the initiation phase of carcinogenesis.

A biometrical study on esophageal invasion of carcinoma of the upper stomach. Part I: Determination of occurring point of the cancer and analysis of its horizontal extension.

In order to detect the occurring point of gastric cancer, and to determine its horizontal extension from this point, we performed a histological examination of 30 resected specimens of upper stomach cancer and 31 of middle and lower stomach cancers. The center of the horizontal extension (Oh) and that of the vertical extension (Ov) were calculated using a paper model. The mean distance between Ov and Oh (Ov-Oh D) was as little as 5.7 +/- 5.0 mm, and the ratio of Ov-Oh D to the size of the lesion was as low as 8.3 +/- 6.7%. There was a linear correlation between the oral and anal radii of the cancer. There was also a linear correlation between anterior and posterior radii of the cancer. In conclusion, either the Oh or the Ov can be considered as the occurring point, and the cancer grows concentrically around this point.

A biometrical study on esophageal invasion of carcinoma of the upper stomach. Part II: Radiographic evaluation of esophageal invasion on the basis of its occurring point and size.

Esophageal invasion of upper stomach cancer was analized on the resected specimen based on its occurring point and size. The distance of esophageal invasion was calculated by subtracting the distance between the occurring point and esophagogastric junction (EJG) from the radius of the cancer on the preoperative X-ray films. Fifty-six (76.7%) out of 73 resected cancers of the upper stomach invaded the esophagus. The average distance of invasion was 19.8 +/- 12.7 mm; the longest distance was 64.0 mm. The shorter was the distance of the occurring point from the EGJ, the longer was the esophageal invasion. The calculated distance of esophageal invasion of the cancer was correlated significantly with its histological distance (p less than 0.01). The distance of esophageal invasion can be seen with acceptable accuracy on the X-ray films preoperatively, even when the proximal edge of esophageal invasion is not clear on the films.

Transabdominal operation for carcinoma of the gastric cardia: application of pulling-up retractor and EEA stapler.

In order to ascertain the advantages of the combined use of the pulling-up retractor and EEA stapler, we reviewed 88 patients who underwent surgery for upper stomach cancer between 1978 and 1986. The length of resected esophagus was significantly longer in patients operated on using an abdominal approach with this combination, as in those using a thoracoabdominal approach, than in those who were operated on using an abdominal approach with only the retractor or without the instruments (p less than 0.05). A relatively high incidence of leakage occurred at the anastomosis of the esophagus to the stomach or jejunum following operation using a transabdominal approach without the instruments. Pulmonary complication tended to be decreased in the non-thoracotomized patients compared to the thoracotomized patients. Postoperative radiogram following the combined use showed an esophagogastrostomy at a high level in the mediastinum. Our combination technique enables lymphadenectomy in the lower mediastinum and a sufficiently long enough resection of the esophagus without fatal complications.

[Evaluation of endoscopic mucosal resection (EMR) as a curative therapy against early gastric cancer].

This study investigated the effectiveness of EMR as a curative therapy against early gastric cancer, comparing with that of radical operation. In 256 radical operation cases, five year survival rates were 97.5% in m-cancer and 93.2% in sm-cancer. In these cases, postoperative complications occurred in 7.8%, with operative mortality being 0.78%. In 56 EMR cases, nine encountered slight bleeding, which was controlled by ethanol injection under endoscopy. Regarding prognosis of EMR, cancer recurrences occurred in 45.8% of cases with stump involvement in the resected mucosa (stump (+)). In cases without stump involvement in the resected mucosa (stump (-)), no recurrence were found except one case, in which distance from the cancer edge to the stump was only 0.6 mm, suggesting that enough distance (2mm) to the stump is required for curative EMR. Stump (-) rate was high (81.2%) in cases of small cancer less than 1 cm in diameter, but was low in cases of cancer greater than 2 cm and those located in upper body or lesser curvature. To establish EMR as a curative therapy, it must be performed by single collection to check remaining cancer. In conclusion, although radical operation is still the standard curative therapy, EMR should be considered as an alternative therapy.

[Effect of gastrectomy on release of gut hormones].

We investigated the effect of gastrectomy on the digestive system in 87 postoperative long-term survivors under test meal or egg yolk load. After test meal, gastrin and secretin responses were decreased in each of groups of proximal gastrectomy (PG), distal gastrectomy with Billroth-I (DG-B1), that with Billroth-II (DG-B2), total gastrectomy with interposition (TG-I), and that with Roux-Y (TG-RY). However, sufficient acid-secretors after partial gastrectomy showed secretin responses comparable to controls. Furthermore, cases of total gastrectomy given betain-hydrochloride with test meal increased secretin responses. Serum glucose response was higher in the TG-RY group while insulin response was high in the TG-RY and DG-B2 groups, compared with controls. GLI response was high in all groups compared with controls. Postgastrectomy gallstone occurred in 11.6%. Yolk-induced contraction of the gallbladder was decreased, and CCK release increased, for several years postoperatively. Gallbladder contraction with CCK was reduced for one year postoperatively. The contraction was reduced in persons with gallstone than those without it. This study shows that the digestive function after gastrectomy depends on acidification and duodenal passage of food, and that reduced contraction with CCK plays an important role in hypokinesis of the gallbladder.

[Endoscopic hemostasis against hemorrhage from the upper gastrointestinal tract: its indication and limitation].

We reviewed endoscopic hemostasis that had been performed upon 353 acutely hemorrhagic peptic ulcer cases: Among them, 145 received thrombin spraying; 36, electrocoagulation; 145, topical injection of ethanol; and 27, topical injection of aetoxyscrelol. Hemostasis lasting for more than 24 hours after the treatment was defined as transient hemostasis, and hemostasis lasting for more than two weeks, as permanent hemostasis. The overall rate of transient hemostasis was 87.5%; 84.8% by thrombin spraying, 83.4% by electrocoagulation, 89.0% by injection of ethanol, 100% by injection of aetoxyscrelol, respectively. The overall rate of permanent hemostasis was 71.1%; 75.9% by thrombin spraying, 58.3% by electrocoagulation, 69.7% by injection of ethanol, 70.4% by injection of aetoxyscrelol, respectively. The rate of emergency operation for bleeding was reduced to 9.9% after the induction of endoscopic hemostasis from 64.0% before the induction. The mortality was also reduced to 3.1% from 8.9%. Particularly, over the last 4 years, the emergency operation and the mortality have been reduced, accounting from 7.2% and 2.2%, respectively. In conclusions, thrombin spraying is the first choice for mild and diffuse hemorrhage, and topical injection of ethanol is indicated for hemorrhage from exposed vessels and for localized hemorrhage.

[Estrogen dependent plasminogen activator in breast cancer cells; experimental and clinical studies].

Hormonal regulation of plasminogen activator (PA) in rat mammary tumor induced by 7,12-dimethylbenz (a) anthracene (DMBA) was studied both in vivo and in vitro. PA activity in DMBA-tumor was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide and tamoxifen. Furthermore DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that estrogen might regulate de novo synthesis of PA at a transcriptional level via an estrogen receptor system, and that this hormone might support the growth of DMBA-tumor into adjacent tissues by inducing PA in a direct manner via a route distinct from a prolactin pathway. To examine whether PA reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors. The results strongly suggest that PA can be used as an effective functional marker for hormone dependence in human breast cancer.

Histopathologic study on development and extension of atrophic change in the gastric mucosa.

A histopathologic study was carried out on 30 resected stomachs with various gastric or duodenal diseases. Both the pyloric gland cells and the parietal cells were counted in serial sections of the surgically resected stomach. A good correlation (p less than 0.001) was found between the number of pyloric gland cells and parietal cells. The number of both glandular cells was greatest on the greater curvature and fewest at the part closer to the antrofundic mucosal border on the lesser curvature. In addition, a fairly uniform pattern was observed in the distribution of the parietal cells. The maximum density area of parietal cells was centered on the greater curvature of the stomach body, and this density decreased concentrically in proportion to the distance from the center. This uniform pattern was seen in almost all specimens, with or without atrophic change in the gastric mucosa. These results suggest that atrophic change does not develop in a particular part of the stomach but wholly and equally in the gastric mucosa.

Role of antral mucosa in intestinal phase of gastric secretion in dogs.

This study was performed to investigate the mechanisms and significance of the intestinal phase of gastric secretion. With infusion of 10% liver extract into the duodenum of dogs, serum gastrin levels of the right gastroepiploic vein increased significantly (p less than 0.01). With infusion of the pH 7.0 liver extract, acid and pepsin outputs in non- antrectomized dogs increased significantly (p less than 0.01), as did serum gastrin levels (p less than 0.01). Post-infusion acid output in these dogs was 48 +/- 16% of tetragastrin-stimulated output. With the same infusion, antrectomized dogs showed no significant increase of acid and pepsin outputs and serum gastrin levels. Acid output and serum gastrin levels in non- antrectomized dogs that were infused with pH 2.0 liver extract did not increase significantly. The values of almost all serum amino acids in both types of dogs increased slightly, but insignificantly, with pH 7.0 liver extract. We obtained the following conclusions. The intestinal phase of gastric secretion operates by the mediation of the antral mucosa, from which gastrin is released. Although this phase has some effect, the acid-secretory ability of this phase is masked by inhibitory systems under certain physical conditions.

A specific gastrin receptor in human gastric mucosa.

Biological active 125I-synthetic human gastrin (125I- SHG ) appeared to bind specifically on human gastric mucosal membrane preparations. Gastrin binding was reversible, saturable and of high affinity (Kd = 3.44 +/- 3.44 X 10(-10)M) with the binding site (3.66 +/- 0.34 fmol/mg protein) at 37 degrees C for 30 min (pH 7.4). Specific gastrin binding was present in the fundic mucosa and absent from the antral, duodenal, jejunal, and colonic mucosa. Gastrin analogues (tetragastrin, pentagastrin, caerulein, and synthetic human gastrin) inhibited 125I- SHG specific binding. However, the specific gastrin binding was not inhibited by glucagon, insulin, acetylcholine, atropine, histamine, or cimetidine. It was suggested that gastrin and histamine H2 receptor or gastrin and muscarinic cholinergic receptor did not share the same locus.

A study on the distribution of G-cells in human gastric mucosa.

The distribution of G-cells in the gastric glands was studied quantitatively using the indirect immunoperoxidase method in 37 resected stomachs: 11 for esophageal cancer, 14 for gastric cancer, 4 for gastric ulcer, 7 for duodenal ulcer, and 1 for atypical epithelium. G-cells were seen in the pyloric glands and in the pseudopyloric glands in the atrophic fundic gland area. No G-cells were found in the fundic glands or in the cardiac glands. There was a significant correlation between the number of G-cells and the pyloric and/or pseudopyloric glandular tubes (p less than 0.01). The number of G-cells per glandular tube was 1.9 +/- 0.5 in the pyloric glands and 1.2 +/- 0.4 in the pseudopyloric glands on the pyloric part of the atrophic fundic gland area. G-cells were rarely seen in the pseudopyloric glands on the cardiac part of the atrophic fundic gland area. It is suggested that the pseudopyloric glands without G-cells in the cardiac region are akin to cardiac glands.

Rapid long tube intubation of the jejunum--an improved technique.

This study details improvements in the intubation of a long intestinal decompression tube by use of a new flexible tip guide wire and a new intestinal decompression tube. The intubation route of the endoscope was changed from the oral to the nasal cavity. Although the guide wire formerly used (TGBD-65-345) could be inserted into the descending part of the duodenum by passing it through the biopsy channel of the endoscope, with this new method, the guide wire (TGBD-65-450) could be inserted into the upper jejunum. The endoscope could also be left in the stomach, when this method was used. The long tube was introduced along this guide wire into the upper jejunum. As a result of these improvements, the intubation rate for long intestinal decompression tubes was significantly more rapid and the time reduced. Intubation rate to the jejunum was 96 percent successful, as compared with a former success rate of 75 percent. The intubation time was decreased to 11.3 +/- 5.6 min. to the duodenum and 18.6 +/- 8.6 min. to the upper jejunum. This differs markedly from the former method which required 16.0 +/- 5.3 min. and 39.6 +/- 22.7 min, respectively.

Changes of alveolar stability and phospholipids in pulmonary surfactant in acute pancreatitis.

We investigated changes of alveolar stability and phospholipids in the pulmonary surfactant in case of acute pancreatitis induced in rats. Alveolar stability was examined by recording the pressure-volume relationship. The lung volumes during deflation decreased significantly at equivalent transpulmonary pressures, particularly when the pressure was lower than 6 cm H2O. Bubble stability ratio and surface tension indicated that the surface activity of the pulmonary surfactant did decrease in the rats with acute pancreatitis. The alveolar phospholipid content decreased, and the lecithin fraction also decreased significantly, as compared to the control groups. The metabolism of alveolar lecithin was examined following intravenous administration of 14C-labeled palmitate. The biological half-life of the radioactivity of alveolar lecithin was approximately 6 hours in the pancreatitis group, 12 hours in the hepatic ducts ligated group and 14 hours in the simple laparotomy group. The degradation of alveolar lecithin, as well as its synthesis, was accelerated in the rats with acute pancreatitis. However, a decrease in alveolar phospholipid, mainly in lecithin fraction, indicated that the synthesis was inadequate to maintain normal levels and the impairment in pulmonary surfactant may result in a respiratory insufficiency.

The histogenesis of DMH-induced colonic carcinoma in rats.

Twenty-one Donryu male rats of six weeks old were injected with 1,2-dimethyl-hydrazine hydrochloride (DMH), once a week, for 4 to 20 weeks, and sacrificed at intervals of two weeks since a lapse of four weeks after the commencement of the injections. The DMH induced 320 atypia lesions, from 0.03 through 20 mm in size, of grade II or higher. The rate of benign lesions was higher in the group receiving less than 20 injections than in the group of 20 injections of DMH, while in the latter group, the rates of the benign, borderline and malignant lesions were stable, suggesting that benign lesions mainly develop in the earlier period of the DMH treatment, and thereafter various grades of lesions develop at a constant rate. All the benign lesions were less than 1 mm in size, and all lesions greater than 1 mm were malignant. In addition, the size of the lesion was significantly greater when it was occupied by malignant crypts in a greater rate. These results indicate that the benign lesions become cancerous before they reach a certain size (adenoma-carcinoma sequence). Twenty-seven minute lesions (less than 1 mm) were mixed lesions of malignant and benign atypia, suggesting that the adenoma-carcinoma sequence is elicited in any size of lesion. On the other hand, there were 41 minute malignant-only lesions, which constituted 27.7% of the overall minute lesions and included three "single crypt" cancers. In addition, malignant-only lesions were smaller when compared to the malignant-dominant mixed lesions. These results indicate that about 30% of colon cancers develop de-novo.