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Biomedical subjects

D Saito

Publications and source records attributed to D Saito.

At least 55 records · Page 3Linked to original sources

Early gastric stump cancer following distal gastrectomy.

BACKGROUND: Gastric stump cancer (GSC) is usually diagnosed at an advanced stage, and consequently the prognosis is poor. AIMS: To investigate the clinicopathological characteristics of GSC at an early stage to assist in its identification, and thereby improve its prognosis. METHODS: Forty three patients with resected early GSC were compared with 156 patients with resected primary early cancer in the upper third of the stomach. RESULTS: Sixty five per cent (28/43) of the early GSC patients showed the elevated type endoscopically, although the frequency of the depressed type in GSC has tended to increase in the past five years. This occurred in less than 26% (40/156) of the primary early cancers. Half of the early GSCs were located on the lesser curvature (47%), and revealed differentiated adenocarcinoma (81%) histologically. The male:female ratio of early GSC cases was about 6:1, which was much higher than that in patients with primary early cancer. The five year survival rates of patients with early GSCs and early primary cancers were 84% and 95%, respectively. GSC had a favourable prognosis, if it was detected at an early stage. CONCLUSION: To detect early GSC, our results suggest that special attention should be given to elevated as well as depressed lesions on the lesser curvature of the stomach, particularly in men, during endoscopic examinations.

Adenocarcinoma↗

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗

Clinicopathological studies on coexisting gastric malignant lymphoma and gastric adenocarcinoma: report of four cases and review of the Japanese literature.

Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the National Cancer Center Hospital, Tokyo, we found four cases (three males and one female) of adenocarcinoma coexisting in the stomach. The incidence of gastric malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that patients with lymphoma may have an increased incidence of gastric adenocarcinoma. A review of the Japanese literature revealed an additional 62 patients who developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total series of 66 patients whose age and sex were recorded, there were 48 males with a mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most adenocarcinomas were macroscopically early (76%) and of histologically differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type macroscopically. The correct preoperative diagnoses were made in only 27% (16/59) of cases, when both tumors were located independently.

Adenocarcinoma↗

Colonoscopy for frank bloody stools associated with cancer chemotherapy.

Diarrhea is a common complication of cancer chemotherapy, while bloody stool is rare. Pseudomembranous colitis has been reported as causing bloody diarrhea after chemotherapy. In this report, we describe nine consecutive patients who presented frank bloody stools within one month after cancer chemotherapy. Patients with a history of pelvic irradiation or with a previously identified colorectal tumor were excluded. Among nine patients, bleeding from tumor undetected before chemotherapy was seen in three, pseudomembranous colitis in four, ischemic colitis in one and methicillin-resistant Staphylococcus aureus enterocolitis in one. Of the three tumors, one was an adenomatous polyp and the other two were metastatic tumors. Two of the four patients with pseudomembranous colitis had not received antibiotics before the onset of colitis. Causes of bloody stools after chemotherapy were various and colonoscopy played an important role in diagnosis and prompt therapy.

Adenocarcinoma↗

Helicobacter pylori extracts exhibit nicotinamide adenine dinucleotide-derived adenylation but not mono(adenosine 5'-diphosphate-ribosyl)ation of DNA ligase.

The issue of toxins produced by Helicobacter pylori (H. pylori) urgently requires clarification given that the bacterium causes gastric epithelial cell damage which may lead to precancerous and cancerous changes. During an investigation of the possibility of mono(adenosine 5'-diphosphate (ADP)-ribosyl)ation by H. pylori products, as observed for other bacterial toxins, we found that radioactivity of [adenylate-32P]nicotinamide adenine dinucleotide (NAD) is incorporated into an H. pylori protein of 80 kDa after incubation with crude bacterial extract. In contrast, [carbonyl-14C]NAD did not show any radioactivity incorporation. Unexpectedly, treatment of the modified protein with 0.1 N HCl, but not 0.1 N NaOH, released the AMP moiety. Such chemical properties are characteristic of bacterial DNA ligase-AMP complexes. We found that an antibody raised against Escherichia coli DNA ligase [EC 6.5.1.2] immunoprecipitated the modified 80 kDa protein. Our results indicate that incorporation of radioactivity derived from NAD into the 80 kDa protein was due to adenylation, but not mono(ADP-ribosyl)ation, of the DNA ligase of H. pylori.

Adenosine Diphosphate Ribose↗

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗

Effects of coronary blood flow, myocardial contractility, and heart rate on cardiac lymph circulation in open-chest dogs. Use of a direct cannulation method for subepicardial lymph vessel.

The study was conducted to evaluate the effects of increased coronary blood flow (CBF), myocardial contractility, and heart rate on cardiac lymph circulation using a subepicardial lymph channel in anesthetized open-chest dogs. A subepicardial lymph vessel along the left anterior descending coronary artery (LAD) was cannulated directly with a small polyethylene tube, and lymph flow (LF) and protein concentration of lymph (PC) were measured. Coronary blood flow (CBF) was increased with intracoronary infusion of adenosine, and myocardial contractility with isoproterenol (isoprenaline) infusion. Effects of an increase in CBF using a constant flow system were also studied. Heart rate was increased by atrial pacing. The control cardiac LF in 17 adult mongrel dogs varied from 5.3 to 12.6 microliters/min (mean 8.4 +/- 2.8). With an increase in CBF, LF and protein efflux to lymph (PEF) increased both adenosine and isoproterenol infusion, while PC was decreased by adenosine and increased by isoproterenol. The increase in CBF using the constant flow system elicited the essentially similar extent of changes in LF and PC in relation to a change in CBF as those during infusion of adenosine. The increase in LF and PEF was significantly smaller during the infusion of adenosine than isoproterenol infusion in relation to a change in CBF. In contrast, pacing-induced tachycardia which caused a relative shortening of the diastolic phase in the heart cycle reduced LF and PEF despite of a slight increase in CBF. These findings suggest that CBF and relative duration of diastole in the heart cycle play an important role in regulation of lymph circulation, and isoproterenol can change capillary permeability in addition to increasing CBF.

Adenosine↗

Risk factors for lymph node metastasis from intramucosal gastric carcinoma.

BACKGROUND: Although regional lymph node metastasis from intramucosal early gastric carcinoma (EGC) is rare, it is very important to clarify the characteristics of patients having lymph nodal metastases in order to determine appropriate therapy. METHODS: The authors investigated 1196 patients with solitary intramucosal EGC who underwent resection at the National Cancer Center Hospital in Tokyo, with special reference to lymph node metastases. Eight clinicopathologic factors (age, sex, tumor: size, location, macroscopic type, histologic type, histologic ulceration of the tumor, and lymphatic vessel invasion) were investigated by univariate and multivariate analyses for their possible relationship to lymph node metastasis. RESULTS: Lymph node metastases were found in 43 patients (3.5%). Univariate analysis revealed that younger age (< 57 years), macroscopic depressed type, larger tumor size (> or= 30 mm), undifferentiated histologic type, histologic ulceration of the carcinoma, and lymphatic vessel invasion had a significant association with regional lymph node metastasis. Multivariate analysis revealed that lymphatic vessel invasion, histologic ulceration of the tumor, and larger size (> or = 30 mm) were independent risk factors for regional lymph node metastasis. The incidence of lymph node metastasis from intramucosal EGC negative for these 3 risk factors was only 0.36% (1 in 277 patients). CONCLUSIONS: Lymphadenectomy is unnecessary for patients with small intramucosal EGC with neither histologic ulceration of the tumor nor lymphatic vessel invasion because the incidence of regional lymph node metastasis is extremely low in those patients. The therapeutic options for such patients would be local resection or endoscopic resection.

Age Factors↗

An early phase II study of etoposide (VP-16) in advanced gastric cancer.

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.

Adenocarcinoma↗

Circulating parathyroid hormone-related protein (109-141) in malignancy-associated hypercalcemia.

For differential diagnosis between hypercalcemia-induced bone metastasis and humoral hypercalcemia of malignancy (HHM), serum parathyroid hormone-related protein (PTHrP) concentrations were measured in normal subjects and patients with malignancy-associated hypercalcemia according to the presence or absence of bone metastasis, using a new sensitive PTHrP(109-141) radioimmunoassay system. The serum PTHrP(109-141) levels in all of 14 patients without bone metastasis were significantly higher than those in normal subjects. However, in four patients with hypercalcemia associated with bone metastasis the levels were nearly the same as those in normal subjects. The time course in two hypercalcemic patients with esophageal carcinoma revealed that serum PTHrP(109-141) levels were elevated before hypercalcemia developed and that changes in PTHrP(109-141) and corrected serum calcium levels were significantly correlated. These findings suggest that determination of serum PTHrP(109-141) may be clinically important not only for differential diagnosis of HHM but also as a useful predictive marker of hypercalcemia.

Adolescent↗

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Animals↗

[Epicardial lipoma].

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Diagnosis, Differential↗

Apical hypertrophy associated with rapid T wave inversion on the electrocardiogram.

A 53-year-old man who had no chest pain and no family history of heart disease demonstrated a rapid T wave change on an electrocardiogram, from a positive T wave to a giant negative T wave, within 1 year. Echocardiography showed no left ventricular hypertrophy before or after the T wave change. Cine-magnetic resonance imaging revealed focal apical hypertrophy after the appearance of the giant negative T wave. Although T wave inversions sometimes develop within a short period in patients with hypertrophic cardiomyopathy, they are rare in a patient without hypertension or chest pain.

Arrhythmias, Cardiac↗

Clinicopathologic features of early rectal carcinoma and indications for endoscopic treatment.

PURPOSE: This study was undertaken to clarify the indications for endoscopic treatment. METHODS: Clinical and pathologic features of 191 lesions in 180 patients with early rectal carcinoma were examined, including 110 intramucosal carcinomas and 81 carcinomas with submucosal invasion (submucosal carcinomas). All lesions had been endoscopically or surgically resected at the National Cancer Center Hospital between 1976 and 1990. RESULTS: Metastasis to regional lymph nodes (LN metastasis) was seen in 0 percent (0/39) of intramucosal carcinomas and 9.2 percent (6/65) of submucosal carcinomas in the surgically treated patients. The incidence of LN metastasis was higher for lesions larger than 10 mm in diameter, for those showing massive submucosal invasion, and for moderately differentiated adenocarcinomas. LN metastases were associated significantly with lymphatic invasion. CONCLUSIONS: These results suggest that early rectal carcinomas should be resected surgically if they 1) show massive submucosal invasion, 2) are classified as moderately differentiated adenocarcinomas, and 3) are larger than 10 mm in diameter. In patients with both scanty submucosal invasion and features of well-differentiated adenocarcinoma or intramucosal carcinoma and if no other risk factors for LN metastasis are present, such as lymphatic invasion by the primary lesion, surveillance may suffice after endoscopic resection.

Adult↗

Identification of mycobacteria by nonradioisotopic single-strand conformation polymorphism analysis.

Clinical isolates of mycobacteria were identified to species levels using nonradioisotopic single-strand conformation polymorphism (non-RI SSCP) analysis of 16S rRNA gene fragments amplified by polymerase chain reaction with primers common to all of mycobacterial species. The method is based on a hypervariable region within the 16S rRNA in mycobacteria, which is characterized by species-specific nucleotide sequences. A total of 92 mycobacterial strains (Mycobacterium tuberculosis, M. avium, M. gordonae, M. intracellulare, M. kansasii, M. chelonae, M. nonchromogenicum, M. xenopi, and unidentified strain) were studied. They were classified into nine types of pattern showing single-strand DNA bands having different mobilities. Each strain was shown in the species-specific mobility by non-RI SSCP analysis. The results of non-RI SSCP analysis were identical to those of standard biochemical methods and 16S rRNA sequencing.

DNA Primers↗

Helicobacter pylori infection, serum pepsinogen level and gastric cancer: a case-control study in Japan.

We conducted a case-control study to evaluate the effect of Helicobacter pylori (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No significant association was observed in all sets [matched odds ratio (OR) = 1.04, 95% confidence interval: 0.73-1.49]. In subgroup analyses, however, an association was suggested in females [OR = 1.57], a younger population (< 50 years) [OR = 1.86], early cancer [OR = 1.53] and small cancer (< 40 mm) [OR = 1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an increase in age or cancer growth (depth of tumor invasion and tumor size). Considering that the spontaneous disappearance of HP due to extended mucosal atrophy may lead to these decreasing odds ratios, we applied the conditional logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis. This analysis showed a positive association with HP infection in all sets [OR = 1.69; 1.01-2.81], distal cancer [OR = 1.88; 1.07-3.31] and intestinal-type cancer [OR = 3.76; 1.39-10.18]. We concluded that the risk of cancer associated with HP infection may be underestimated in studies with cross-sectional exposure because of spontaneous disappearance of HP due to extended mucosal atrophy.

Adult↗