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N Uedo

Publications and source records attributed to N Uedo.

17 recordsLinked to original sources

A new method of diagnosing gastric intestinal metaplasia: narrow-band imaging with magnifying endoscopy.

BACKGROUND AND STUDY AIMS: With endoscopy, there is a high rate of interobserver variability in the identification of gastric intestinal metaplasia, and the endoscopic findings correlate poorly with the histological findings. Previous studies by our group investigating the use of a narrow-band imaging system with magnifying endoscopy (NBI-ME) in the gastric mucosa suggested that the appearance of a light blue crest (LBC) on the epithelial surface may be a distinctive endoscopic finding associated with the presence of intestinal metaplasia. The aim of the present study was to clarify the value of NBI-ME for diagnosing gastric intestinal metaplasia. PATIENTS AND METHODS: The LBC was defined as a fine, blue-white line on the crests of the epithelial surface/gyri. To investigate the histology underlying the appearance of LBC, 44 biopsy specimens were obtained from regions containing LBC and 44 from non-LBC mucosa in 34 patients with atrophic gastritis. Three endoscopists then carried out NBI-ME in 107 consecutive patients to validate the diagnostic accuracy of the novel endoscopic technique. The degree of correlation between the LBC grading and the histological parameters of intestinal metaplasia was then assessed. RESULTS: The LBC grading correlated with cells that were positive for CD10 ( P = 0.0001) and Alcian blue ( P = 0.036). The appearance of LBC correlated with histological evidence of intestinal metaplasia with a sensitivity of 89 % (95 % CI, 83 - 96 %), a specificity of 93 % (95 % CI, 88 - 97 %), a positive predictive value of 91 % (95 % CI, 85 - 96 %), a negative predictive value of 92 % (95 % CI, 87 - 97 %), and an accuracy of 91 % (95 % CI, 88 - 95 %). CONCLUSIONS: In narrow-band imaging with magnifying endoscopy, observation of a light blue crest on the epithelial surface in the gastric mucosa is a highly accurate sign of the presence of histological intestinal metaplasia.

Adult↗

Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression.

BACKGROUND: The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia. AIM: To examine CDX2 expression in the non-cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia. METHODS: Sixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining. RESULTS: Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7-18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001). CONCLUSIONS: Loss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.

Aged↗

Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer.

BACKGROUND: In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density. AIM: The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer. METHODS: We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age-matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA. RESULTS: Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded-type group than in the depressed-type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases. CONCLUSIONS: Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.

Aged↗

Attenuation by ambroxol of monochloramine-enhanced gastric carcinogenesis: a possible prevention against Helicobacter pylori-associated gastric carcinogenesis.

The effects of combined administration of a reactive oxidant, monochloramine, and a mucoregulatory agent, ambroxol, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without subcutaneous injection of ambroxol at high or low doses, until the end of the experiment at week 52. Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers at week 52, whereas concomitant administration of ambroxol with ammonium acetate and sodium hypochlorite significantly attenuated this enhanced gastric carcinogenesis. Results also revealed that ambroxol scavenged monochloramine. Because monochloramine is closely related to Helicobacter pylori-associated gastric carcinogenesis, these findings suggest that ambroxol may prevent H. pylori-associated gastric carcinogenesis.

Ambroxol↗

Induction by bombesin of peritoneal metastasis of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

BACKGROUND: We investigated the effect of the gastrointestinal regulatory peptide, bombesin, on the development of peritoneal metastasis from gastric cancers induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on Rho activity in the gastric cancers. METHODS: Rats were allocated to three groups. All groups received MNNG (100 micrograms/ml) solution for 25 weeks from the start of the experiment. Group 1 (controls) received olive oil injections from the start of MNNG treatment; group 2 animals received alternate-day s.c. injections of bombesin (40 micrograms/kg body weight) in olive oil from the start of the experiment until the end of the experiment at week 52; and group 3 received the s.c. bombesin injection on alternate days from week 26 until week 52. The effect of bombesin on Rho activity in gastric cancer was examined by Western blotting. RESULTS: Bombesin given from the start of the experiment (group 2) and after the MNNG treatment (group 3) both significantly increased the incidence of gastric cancer metastasis, compared with controls, at week 52: The incidence of metastasis was significantly higher in group 2 than in group 3. Bombesin from the start of the experiment (group 2) significantly increased the incidence of tumors with deeper invasion or more infiltrative growth pattern, or lymphatic vessel tumor invasion, while bombesin after MNNG treatment (group 3) significantly increased the incidence of lymphatic vessel invasion. Bombesin also increased the activity of Rho protein in the tumors. CONCLUSION: Bombesin significantly increased the incidence of peritoneal metastasis from gastric cancers through the activation of Rho protein.

Animals↗

K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid.

The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation.

Administration, Oral↗

Endoscopic piecemeal resection with submucosal saline injection of large sessile colorectal polyps.

BACKGROUND: Because endoscopic en bloc resection of large, sessile colorectal polyps is technically difficult, they are usually resected piecemeal. However, piecemeal resection makes it difficult to evaluate the completeness of the resection histopathologically. In this study the efficacy of endoscopic piecemeal resection of large, sessile colorectal polyps was investigated after follow-up greater than 1 year. METHODS: We removed 56 sessile colorectal polyps 2 cm or greater in diameter in 56 patients by using an endoscopic submucosal saline injection technique. Endoscopic examinations were repeated at 3, 6, and 12 months and longer after initial endoscopic resection. If no residual tumor was found endoscopically and histologically, the patient was considered to be "cured." RESULTS: Of the 56 polyps, 14 (25%) were resected en bloc, and 42 (75%) were resected piecemeal. Of the 42 patients treated with piecemeal resection, 23 (55%) required additional endoscopic or surgical interventions. In patients followed 1 year or longer after initial treatment, the cure rate by en bloc resection was 100% (14 of 14) and that by piecemeal resection was 83% (35 of 42). Arterial bleeding occurred in 4 patients (7%) during or after endoscopic resection. In 3 of them, bleeding was stopped by endoscopic clipping, but 1 patient required emergent laparotomy. CONCLUSIONS: Endoscopic piecemeal resection after submucosal saline injection with an intensive follow-up program is a safe and effective treatment for large, sessile colorectal polyps.

Adult↗

Effectiveness of endoscopic mucosal resection with submucosal saline injection technique for superficial squamous carcinomas of the esophagus.

BACKGROUND: Intraepithelial cancers (m1 cancer) and cancers that penetrate the basement membrane but do not approach the muscularis mucosae (m2 cancer) do not have lymph node metastasis and thus can be removed completely with mucosal resection. Therefore, in this study, the effectiveness of endoscopic mucosal resection with submucosal saline injection for removal of superficial esophageal cancers was investigated prospectively. METHODS: Twenty-five superficial esophageal cancers in 21 patients were removed with submucosal saline injection. When it was thought that a tumor had not been completely resected en bloc, it was removed completely in piecemeal fashion. Endoscopy was repeated 1, 3, 6, 12 months or more after endoscopic resection. RESULTS: All superficial esophageal cancers were completely removed: 18 (72%) en bloc and 7 (28%) by piecemeal resection. No recurrence was found during a mean observation period of 2.0 years (range 0.8 to 3.6) after resection. Bleeding occurred in 5 cases (24%) during or after resection but was successfully treated with the endoscopic alginate or thrombin spray technique. There was no perforation. CONCLUSION: Endoscopic mucosal resection with submucosal saline injection is effective for removal of superficial cancers of the esophagus.

Aged↗

Measurement of carcinoembryonic antigen in colonic effluent as a high-risk marker for colorectal carcinoma.

We evaluated the usefulness of carcinoembryonic antigen (CEA) concentrations in colonic effluent as a high-risk marker for colorectal carcinoma (CRC). After 213 patients ingested 1,800 ml of a 5% isotonic solution of magnesium citrate, colonic effluent was collected from them before routine colonoscopy from February through June 1992. Of these patients, 27 who had undergone colonoscopy after a mean of 2.6 years were selected as subjects. The relationship between the CEA concentration in the colonic effluent and the occurrence of new colorectal tumors was examined. The CEA concentration in colonic effluent was adjusted on the basis of alkaline phosphatase activity. New colorectal tumors were noted significantly more frequently (P = .006) in patients with a high CEA level in colonic effluent (5 of 5; 100%) than in those with low a CEA level (6 of 22; 27%). The CEA concentration in colonic effluent is a simple and practical biomarker for identification of patients at high risk for CRC.

Age Factors↗

Inhibition by rat C-erbB-2/neu antisense oligonucleotide of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of a rat C-erbB-2/neu (C-erbB-2) antisense oligonucleotide on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labeling and apoptotic indices of gastric cancer was examined in Wistar rats After oral treatment with MNNG for 25 weeks, the rats received intraperitoneal injections of a C-erbB-2 antisense-liposome complex or a sense-liposome complex at a dose of 50 microgram oligonucleotide/kg body weight every other day until the end of the experiment in week 52. In week 52, the incidence of gastric cancers was significantly lover in rats treated with the C-erbB-2 antisense oligonucleotide than in rats treated with the sense oligonucleotide. Administration of the C-erbB-2 antisense oligonucleotide also significantly decreased the bromodeoxyuridine-labeling index and significantly increased the apoptotic index of gastric cancers. The mean cellular fluorescence of gastric antral cells in MNNG-treated rats was positively correlated with the dose of FITC-labeled C-erbB-2 antisense oligonucleotide. Our findings indicate that the antisense oligonucleotide inhibits gastric carcinogenesis through decreased cell proliferation and increased apoptosis induction and suggest that antisense strategies may provide new treatment for gastric cancer.

Animals↗

Attenuation by d-limonene of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of prolonged administration of d-limonene, a monocyclic monoterpene, on sodium chloride-enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine, the labeling and apoptotic indices, and ornithine decarboxylase (ODC) activity of gastric cancers were investigated in Wistar rats. After 25 weeks of carcinogen treatment, rats were given chow pellets containing 10% sodium chloride and 1% limonene ad libitum. In week 52, the incidence of gastric cancers, the labeling index and ODC activity were significantly higher and the apoptotic index was significantly lower in rats given sodium chlolide than in untreated control rats. However, in rats given both sodium chloride and d-limonene, the incidence of gastric cancers, the labeling index and ODC activity were significantly lower and the apoptotic index was significantly higher than in rats given sodium chloride alone. Our findings suggest that limonene attenuates the gastric carcinogenesis enhanced by sodium chloride via increased apoptosis and decreased ODC activity in gastric cancers.

Animals↗

Inhibition by D-limonene of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged oral administration of D-limonene on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labeling and apoptotic indices of gastric cancers were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were given chow pellets containing 1% or 2% limonene. In week 52, long-term oral administration of 2%, but not 1%, limonene significantly decreased the incidence of gastric cancers. Limonene also significantly decreased the labeling index and significantly increased the apoptotic index of gastric cancers. No K-ras mutations were detected in gastric cancers induced by MNNG in either group. These findings indicate that limonene inhibits the development of gastric cancers through increased apoptosis and decreased DNA synthesis of gastric cancers, but not through ras oncoprotein plasma membrane association.

Adenocarcinoma↗

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori.

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.

Adult↗

Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations.

OBJECTIVE: Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease. METHODS: Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas. CONCLUSIONS: It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.

Aged↗

Effectiveness of premedication with pronase for improving visibility during gastroendoscopy: a randomized controlled trial.

BACKGROUND: Minute early gastric cancers can be removed with endoscopic mucosal resection techniques. However, early detection of these minute cancers with endoscopy is still difficult. For this purpose, use of a dye is helpful. To increase visibility further, gastric mucus should be removed before endoscopic examination. In this study, the effectiveness of premedication with pronase for improving visibility during gastroendoscopy was investigated. METHODS: From January through July 1996, outpatients scheduled for gastroendoscopy were randomly assigned to oral premedication with the antifoam agent dimethylpolysiloxane alone (n=34), with dimethylpolysiloxane plus sodium bicarbonate (n=32), or with dimethylpolysiloxane, sodium bicarbonate, and pronase (n=34). All were given about 10 minutes before the start of endoscopy. After inserting the endoscope, the endoscopist gave visibility scores at conventional endoscopy and after methylene blue spraying. RESULTS: Premedication with pronase significantly improved visibility before and after methylene blue spraying as compared with the two other groups pretreated without pronase. Pronase also significantly shortened the times for chromoendoscopic examination. Pronase had no significant effect on the culture of Helicobacter pylori. CONCLUSION: Premedication with pronase improved endoscopic visualization during conventional endoscopy and chromoendoscopy. Its routine use at gastroendoscopy is therefore recommended.

Adult↗

Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy.

BACKGROUND/AIMS: Cytological examination of pancreatic juice is useful in the diagnosis of an occult cancer of the pancreas. The early diagnosis of pancreatic carcinoma using traditional radiographic or ultrasonographic methods is extremely difficult. METHODOLOGY: In order to detect an early pancreatic cancer, cytological examination, measurement of tumor marker, and detection of K-ras point mutation were performed using the samples of pure pancreatic juice aspirated endoscopically in patients who had symptoms or findings that suggested pancreatic disease. RESULTS: By routine ERP-cytology, positive cytologic results were obtained in 15 (4%) out of 359 patients without a mass. With the aid of intra-operative cytodiagnosis, all 15 occult neoplasms of the pancreas were successfully resected. One patient died from another disease without evidence of recurrence. However, the other patients were alive with no evidence of recurrence for an average of 5.5 years following surgery. The patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. The CEA levels in the pure pancreatic juice were significantly higher in patients with pancreatic cancer than in those with pancreatitis. K-ras point mutation at codon 12 was detected not only in cases of pancreatic cancer, but also in cases of chronic pancreatitis as well as control subjects. CONCLUSIONS: Cytological examination of pancreatic juice is useful in the diagnosis of an early and potentially curable in situ cancer of the pancreas. The CEA levels in the pure pancreatic juice provided useful information for differentiating the pancreatic cancer from chronic pancreatitis. K-ras point mutation at codon 12 in pancreatic juice was considered to be useful in identifying patients at high risk for the development of pancreatic cancer.

Aged↗

Endoscopic resection with a two-channel videoendoscope for gastric carcinoid tumors.

BACKGROUND/AIMS: Endoscopic resection has been used to treat hypergastrinemia-associated early carcinoid tumors of the stomach. However, indications for endoscopic treatment of these tumors have not been established. Moreover, endoscopic resection of these tumors is often difficult with conventional polypectomy, because these tumors are often located in the submucosal layer. To completely remove these tumors, we used a two-channel videoendoscope with which both grasping forceps and a polypectomy snare could be used simultaneously. METHODOLOGY: At Osaka Medical Center for Cancer and Cardiovascular Diseases, eight carcinoid tumors in six patients were removed with a two-channel videoendoscope. Reports of early carcinoid tumor in Japanese literature were reviewed to analyze the relationship between lymph node metastasis and the size and depth of involvement of these tumors. RESULTS: Six carcinoid tumors were completely removed "en bloc", but two tumors were incompletely removed. In these two patients, submucosal tumor invasion was observed on the excision line. To completely remove these tumors, the oral side, but not the top, of the tumor should be strongly grasped and pulled toward the center of the lumen as far as possible by the grasping forceps, which had been passed through the snare loop. Endoscopic follow-up studies showed no local recurrence in any patients with and without complete tumor resection during the average observation period of 30 months. A review of histological reports in Japanese literature showed that lymph node metastasis did not occur when the tumors were less than 10 mm in diameter, and could be completely removed by an endoscope. CONCLUSIONS: Endoscopic resection with a two-channel videoendoscope is a useful and safe method for resection of small carcinoid tumors of the stomach.

Aged↗