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Biomedical subjects

K Aoyagi

Publications and source records attributed to K Aoyagi.

At least 145 records · Page 8Linked to original sources

Early gastric cancer and lymph node metastasis.

A total of 1,845 cases of gastric cancer have been resected in our hospital during the past 18 years. Of these, 764 cases (41.5%) were early gastric cancer. The rate of lymph node metastasis was 2% in early mucosal cancer and 19.4% in early submucosal cancer (p < 0.001). In the cases of early mucosal cancer, the rate of lymph node metastasis was 0.9% for the elevated type and 2.4% for the depressed type. In the cases of early submucosal cancer, the rate of lymph node metastasis was 25.3% for the elevated type and 17.3% for the depressed type. In the mucosal cancers the rate of lymph node metastasis was high in the 0-IIc and IIc + III macroscopic type, and in the poorly differentiated microscopic type. In the submucosal cancers the rate of lymph node metastasis was 40% in mucinous adenocarcinoma and 33% in papillary adenocarcinoma. There was no lymph node metastasis in any case of early gastric cancer smaller than 1 cm surface diameter.

Adult↗

Gastric cancer surgery in the octogenarian.

Seventy-seven octogenarian patients with gastric cancer (Group 1) were retrospectively investigated and compared with patients of age from 75 to 79 years (Group 2). The incidence rates for renal impairment, hepatic impairment, and hypoproteinemia, as preoperative complications, were higher in Group 1 than in Group 2 (each p < 0.05). The resectability rate was 83% in Group 1 and 89% in Group 2. D1 lymphadenectomy was performed for 45% of Group 1 and for 18% of Group 2 (p < 0.001). On the other hand, D2 lymphadenectomy was performed for 39% of Group 1 and for 71% of Group 2 (p < 0.001). A postoperative complication occurred in 25% of Group 1 and in 9% of Group 2 (p < 0.01). However, the postoperative mortality rate was zero in both groups. The t1 (early cancer) rate was 27% in Group 1 and 41% in Group 2 (p < 0.05). On the other hand, t2 was 31% in Group 1 and 19% in Group 2 (p < 0.05). The overall 5-year-survival rate was 38% in Group 1 and 48% in Group 2. When causes of mortality other than gastric cancer were excluded, the 5-year-survival-rate was 51% in Group 1 and 67% in Group 2 (p < 0.01).

Aged↗

Gastrectomy with combined resection of other organs for carcinoma of the stomach with invasion to adjacent organs: clinical efficacy in a retrospective study.

BACKGROUND: Carcinoma of the stomach invading one or more adjacent organs raises serious concerns over en bloc dissection because en bloc resection has an associated high risk and such advanced carcinoma is frequently associated with incurable factors. Thus, it is important to understand the efficacy of gastrectomy combined with other organ resection and to refine the indications for en bloc dissection. STUDY DESIGN: Seventy-seven patients with carcinoma of the stomach directly invading adjacent organs or structures were analyzed retrospectively to investigate the efficacy of en bloc resection. Forty-one patients underwent gastrectomy combined with resection of one or more invaded organs (combined resection group), while the other 36 patients underwent gastrectomy with palliative abrasion between the primary tumor and the invasion site (noncombined resection group). RESULTS: The five-year survival rate was 23 percent in the combined resection group and 0 percent in the noncombined resection group (p < .05). The 23 curative cases and 18 noncurative cases in the combined resection group had a survival rate of 41 percent and 0 percent, respectively (p < .05). The survival rate after a single organ resection was 29 percent, and after a multiple organ resection, 0 percent (p < .05). Cases of carcinoma invading either the pancreas or mesocolon had a slightly but not significantly better prognosis. In Borrmann type IV carcinoma there was no difference in survival between the curative and noncurative operation. Cases with P1 dissemination had a better prognosis than those of P2 and P3 dissemination. CONCLUSIONS: The best indication for an en bloc combined organ resection was an invasion limited to only one other organ, not more than N2, no incurable factor, and any type except Borrmann type IV. Additionally, an en bloc combined resection would be worth trying for any type of gastric carcinoma with not more than P1 dissemination and with no other incurable factor.

Carcinoma↗

[Application of in situ PCR to clinical pathology--detection of viral infection].

In situ polymerase chain reaction(PCR) combines the sensitivity of solution PCR with the subcellular localization provided by traditional in situ hybridization(ISH). Detection threshold levels for ISH are about 10-20 copies per cell. Therefore rare RNA and DNA sequences are often below detection. PCR is an extremely sensitive technique which amplifies single copy gene sequence to high levels, easily detectable by ISH. Thus, this new technique could have important applications in infectious disease and oncology. Studies on in situ PCR detection of viral DNA sequences include HIV, HPV, CMV, and HBV. The clinical aspects of viral disease have also been studied with a limited number of cases. For example, with HIV, it has been discovered that a larger number of cells previously thought to be uninfected, are latently infected with the virus. In spite of its potentially powerful application for diagnostics, the technique has its own limitation outside research laboratories at present. One of them is a lack of an standardized protocol which can be used for wide range of biological samples. The challenges of this technique and its potential for applications in pathology is discussed.

DNA, Viral↗

[The significance of p21 expression in gastric cancer].

We examined the expression of p53, p21, cyclin D1, E, and PCNA in 75 cases of gastric cancer by immunohistochemical study and the expression of p21 RNA in cases by in situ hybridization. The rate of stage III, IV cases of p53(+) p21(-) group was significantly higher than that of any other groups. The apportinately 3-year survival rate of p53(+) p21(-) group was significantly lower than either that of p21(+) p53(-) or p53(-) p21(-) group. The 3-year survival rates of positive cases were significantly lower than those of negative cases on both cyclin D1 and E. The positive rate of cyclin E of the p53(-) p21(+) group was significantly lower than that of the p53(+) p21(-) group. The average PCNA Labeling. Index (LI) of the p53(+) p21(-) group was significantly higher than that of the p53(-) p21(+) group. The 3-year survival rate of cases with expression of p21 RNA was higher than that of cases without p21 RNA. Average PCNA L1 of cases with expression of mutant-type p53 was high and the number of poor prognostic cases in cases with expression of mutant-type p53 was large. In contrast, the average PCNA LI of cases with expression of p21 was low and the number of good prognostic cases with expression of p21 was large. These results suggest that p21 suppresses synthesis of DNA via cyclin E and PCNA.

Cyclin D1↗

[Analysis of choroidal blood flow by laser speckle flowgraphy].

We applied real-time laser speckle flowgraphy (RLSFG) to quantitate the choroidal circulation. RLSFG was developed utilizing the laser speckle phenomenon. A diode laser, 830 nm in wavelength, serves as the light source. The quantitative index of blood flow velocity is represented as normalized blur (NB), or square blur rate (SBR). This method was applied to the posterior fundus of monkey and human eyes. While one measurement covers a fundus area of 1 mm x 1 mm, it is possible to measure a wider fundus area by montage. The wide color maps showed the architecture of choroidal vessels. It was possible to measure the choroidal blood flow in areas free of major retinal vessels. Application of the method to 3 eyes of retinal artery occlusion and 4 eyes of geographic choroiditis showed that the obtained SBR values in normal fundus is derived 25% from the retinal and 75% from the choroidal circulation. The findings show the potential value of RLSFG in quantitating the choroidal blood flow in situ.

Animals↗

Ménétrièr's disease associated with Helicobacter pylori infection: resolution of enlarged gastric folds and hypoproteinemia after antibacterial treatment.

We herein report a case of a 46-yr-old female with Ménétrièr's disease associated with Helicobacter pylori (H. pylori) infection, in whom the appearance of enlarged gastric folds and hypoproteinemia were both successfully treated by antibacterial treatment. The patient had been treated with famotidine for 3 yr under a diagnosis of Ménétrièr's disease, which caused an increase in her serum protein concentration to a level at which she suffered no clinical problems; however, the concentration never reached a normal range, and the presence of enlarged gastric folds also remained unchanged. Because H. pylori colonization was detected in the stomach and was also retrospectively recognized in the initial histologic specimens, antibacterial treatment with omeprazole, clarithromycin, and metronidazole was thus attempted. As a result of the successful eradication of H. pylori, the enlarged gastric folds returned to normal and the serum protein concentration thus increased to a normal level after the treatment. The etiology of Ménétrièr's disease remains unknown; however, the above findings suggest that H. pylori infection may in some cases cause Ménétrièr's disease and should therefore be carefully treated in any patient with this condition.

Adult↗

Effect of indomethacin suppositories on rectal polyposis in patients with familial adenomatous polyposis.

BACKGROUND: Oral sulindac is known to reduce polyps in patients with familial adenomatous polyposis (FAP). The authors speculated that rectal administration of indomethacin would be effective therapy for adenomas in the rectal remnant of FAP. METHODS: Eight patients with FAP who had been treated by total colectomy with ileorectal anastomosis were administered an indomethacin suppository (50 mg) once or twice daily during a period of 4 or 8 weeks. The number of polyps at the same site within the rectum was counted under proctoscopy prior to, at the end of, and after the treatment. In four patients, proliferative activity of the rectal mucosa was assessed by immunohistochemical staining for MIB-1. RESULTS: In six of the eight patients who initially had ten or more polyps, the number of polyps decreased to fewer than five, whereas such a decrease could not be observed in the remaining two patients. In the six patients, the number of polyps increased after indomethacin was discontinued. The proliferative activity of the rectal mucosa was higher at the end of treatment than it was prior to indomethacin administration. CONCLUSIONS: Indomethacin suppositories may be effective in the management of rectal adenomatosis in patients with FAP.

Adenomatous Polyposis Coli↗

Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer.

We synthesized a potent new antitumor podophyllotoxin derivative (4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin; TOP-53) in our search for a drug that has strong activity against lung cancer and lung metastatic cancer. TOP-53 exhibited twice the inhibitory activity of etoposide (VP-16) against topoisomerase II and induced DNA strand breaks but showed no inhibitory activity against tubulin polymerization. The in vitro cytotoxic activity of TOP-53 assessed as IC50 was 0.016-0.37 microg/ml and 0.26-8.9 microg/ml against marine tumor and human non-small cell lung cancer (NSCLC) cell lines, respectively. TOP-53 exerted significant efficacy equivalent to that of VP-16 on s.c.-implanted murine solid tumors (Colon 26, B16-BL6, and Lewis lung carcinoma) at doses 3-5 times lower than that of VP-16. In human tumor xenografts using NSCLC, TOP-53 was active for four of five tumors, whereas VP-16 was active for two of five tumors. Potent inhibitory activity of TOP-53 was also found against a lung tumor (Lewis lung carcinoma) and four lung metastatic tumors (NL-22 and NL-17 colon cancer, UV2237M fibrosarcoma, and K1735M2 melanoma). TOP-53 appeared to be more active against four of them than VP-16. Thus, TOP-53 is not only active against s.c.-implanted lung cancers but also strongly active against lung localized tumor and metastatic tumors in the lungs. The high selectivity of TOP-53 was attributed to its high distribution into the lung and its persistence. TOP-53 is expected to be highly effective against lung cancer including NSCLC and various lung metastatic tumors in the clinical field.

Animals↗

Visualization of yellowish-orange luminescence from cuprous metallothioneins in liver of Long-Evans Cinnamon rat.

We describe the first use of an emission probe, based on the cuprous thiolate chromophore, for direct microscopical observation of cuprous metallothioneins located in liver of 15-week-old (just before spontaneous hepatitis) Long-Evans Cinnamon rats. The rats show remarkable accumulations of copper and cuprous metallothioneins. In the mildly fixed liver, we visualized the same yellowish-orange luminescence as the specific emission from cuprous metallothioneins, following excitation in 330-385 nm region. In liver from Long-Evans Agouti rat, a counter part of Long-Evans Cinnamon rat, no similar luminescence was found. So, it was thought that cuprous metallothioneins accumulated in the Long-Evans Cinnamon rat liver might emit the yellowish-orange light. To verify this presumption, we tentatively defined three histochemical criteria, quenching tests by oxidation, protonation and mercury treatment, based on the coordination chemical characteristics of metallothioneins. The emission completely satisfied these criteria. Furthermore, the reliability of these criteria was supported by immunocytochemical and biochemical results. Consequently, all results sufficiently indicate that the yellowish-orange luminescence in the Long-Evans Cinnamon rat liver is the emission from cuprous metallothioneins.

Animals↗

Evaluation of the cell kinetics of MNNG-treated rat gastric mucosa based on AgNOR and ODC activity.

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features and cell kinetics in the gastric mucosa of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of gastric mucosa from both MNNG-treated and control rats were histologically examined by staining with nucleolar argylophilic nonhistone (AgNOR) proteins, and their ornithine decarboxylase (ODC) activity was determined every 2 months for 10 months. In 40% of the MNNG-treated rats, atrophy of the gastric mucosa was observed after 2 months, followed by adenomatous proliferation. More AgNOR-positive granules were found in the pyloric glands than in the fundic glands, and the total number of positive granules increased over time. Cancerous and hyperplastic lesions preferentially developed in the pyloric glands and showed significantly more AgNOR-positive granules than the normal mucosa. After 6 months the ODC activity in the MNNG-treated rats was significantly higher than that in the control rats. These results thus suggest that the pyloric glands have a high growth activity, while in addition, adenomatous proliferation is a characteristic pathological feature of precancerous lesions in the stomach in MNNG-treated rats.

Adenocarcinoma↗

Increased numbers of macrophages in noninflamed gastroduodenal mucosa of patients with Crohn's disease.

We investigated immunostained macrophages in the noninflamed mucosa of Crohn's disease patients. Biopsied specimens from endoscopically normal gastroduodenal mucosa of Crohn's disease, ulcerative colitis, and healthy control patients were studied. Sections were examined immunohistochemically using a monoclonal antibody specific for tissue macrophages (CD68). Immunostained mucosal macrophages in the second part of the duodenum, duodenal bulb, gastric antrum, and gastric body of the Crohn's disease group were more numerous than in the ulcerative colitis and control groups. The characteristic findings of Crohn's disease were aggregations, focal subepithelial dense accumulations, and infiltration throughout the mucosa of macrophages not accompanied by a lymphoid infiltrate. The number of macrophages in the gastroduodenal mucosa bore no relationship with the duration of symptoms, clinical activity, or affected site in the intestine. This suggests that the increased number of macrophages in noninflamed mucosa is a histological change characteristic for Crohn's disease that indicates a persistent latent abnormality involving the entire gastrointestinal tract.

Adolescent↗

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats: the role of arterial vagal adrenoceptors.

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through alpha1-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.

Adrenergic Agents↗

The significance of colonic mucosal lymphoid hyperplasia and aphthoid ulcers in Crohn's disease.

OBJECTIVE: To access concordance between radiological severity of aphthae and the more advanced features of Crohn's disease. PATIENTS AND METHODS: In 75 patients with an established diagnosis of Crohn's disease, we evaluated the radiological severity of colonic aphthae by meticulous double-contrast radiography. The degree of aphthae was defined as follows: AE0 = no lesions; AE1 = small nodules without barium flecks (lymphoid hyperplasia); AE2 = minute barium flecks < or = 1 mm in size with a translucent halo (umbilical or eroded lymphoid hyperplasia); AE3 = barium flecks varying from 2 mm to 5 mm in size (typical aphthoid ulcerations). We compared the degree of the lesions to the disease activity, and reviewed these sequential changes during a mean interval of 10 months. RESULTS: AE3 lesions were more prevalent than AE1 or AE2 lesions in patients with active colitis. AE1 or AE2 lesions were found regardless of the involved bowel sites or the disease activity. Of 44 patients receiving a nutritional diet, 26 patients showed regression of the lesions although most of the patients still exhibited AE1 or AE2 lesions. In two of eight patients without the treatment, the lesions progressed. CONCLUSION: In Crohn's disease, development of aphthoid ulcers is associated with disease activity; lymphoid hyperplasia may exist independently of disease activity.

Adolescent↗

Nonpolypoid adenomas of the duodenum in patients with familial adenomatous polyposis (Gardner's syndrome).

BACKGROUND: Although duodenal adenomas are very common in familial adenomatous polyposis, we wished to emphasize our experience with finding nonpolypoid adenomas in the duodenum of patients with this disease. METHODS: Duodenoscopy was performed in 23 patients with an established diagnosis of familial adenomatous polyposis or Gardner's syndrome. RESULTS: Endoscopy revealed single or multiple nonpolypoid adenomas of the duodenum in 7 patients (30%). The lesions were smaller than 5 mm and were endoscopically recognized as flat or depressed reddish lesions; one lesion was completely flat and the remaining lesions were flat-topped elevations with a central depression. All of the lesions were histologically diagnosed as tubular adenoma with moderate epithelial atypia. CONCLUSION: These findings suggest that duodenal nonpolypoid adenomas are common in familial adenomatous polyposis or Gardner's syndrome and that careful surveillance endoscopy seems necessary in patients with this disease.

Adenoma↗