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Biomedical subjects

T Gotoda

Publications and source records attributed to T Gotoda.

At least 19 recordsLinked to original sources
PubMed2007

Cancer of the gastric stump following distal gastrectomy for cancer.

BACKGROUND: Cancer of the gastric stump (CGS) after distal gastrectomy for cancer has not been characterized in a large study. The aim of this study was to investigate the clinicopathological features and outcome of CGS following distal gastrectomy for cancer. METHODS: Patients with CGS following distal gastrectomy for gastric cancer diagnosed between 1970 and 2002 were reviewed retrospectively. RESULTS: A total of 108 patients was identified. The median interval between the initial gastrectomy and resection for CGS was 7.5 (range 1-41) years. The depth of tumour invasion was T1 in 67 patients, T2 in 16, T3 in eight and T4 in 17 patients. Endoscopic mucosal resection was performed in 25 patients with T1 tumours. R0 resection was achieved in 103 patients. The overall 5-year survival rate was 53.1 per cent. The 5-year survival rates for patients with T1, T2, T3 and T4 disease were 76, 40, 13 and 9 per cent respectively. CONCLUSION: The outcome for patients with non-early CGS was poor. Early detection of CGS is important following distal gastrectomy for gastric cancer and strict surveillance is recommended for at least 10 years after the initial gastrectomy.

Adult↗
PubMed2006

Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum.

BACKGROUND: Laterally spreading tumours (LSTs) in the colorectum are usually removed by endoscopic mucosal resection (EMR) even when large in size. LSTs with deeper submucosal (sm) invasion, however, should not be treated by EMR because of the higher risk of lymph node metastasis. AIMS: To determine which endoscopic criteria, including high magnification pit pattern analysis, are associated with sm invasion in LSTs and clarify indications for EMR. METHODS: Eight endoscopic criteria from 511 colorectal LSTs (granular type (LST-G type); non-granular type (LST-NG type)) were evaluated retrospectively for association with sm invasion, and compared with histopathological findings. RESULTS: LST-NG type had a significantly higher frequency of sm invasion than LST-G type (14% v 7%; p<0.01). Presence of a large nodule in LST-G type was associated with higher sm invasion while pit pattern (invasive pattern), sclerous wall change, and larger tumour size were significantly associated with higher sm invasion in LST-NG type. In 19 LST-G type with sm invasion, sm penetration determined histopathologically occurred under the largest nodules (84%; 16/19) and depressed areas (16%; 3/19). Deepest sm penetration in 32 LST-NG type was either under depressed areas (72%; 23/32) or lymph follicular or multifocal sm invasion (28%; 1/32 and 8/32, respectively). CONCLUSIONS: When considering the most suitable therapeutic strategy for LST-G type, we recommend endoscopic piecemeal resection with the area including the large nodule resected first. In contrast, LST-NG type should be removed en bloc because of the higher potential for malignancy and greater difficulty in diagnosing sm depth and extent of invasion compared with LST-G type.

Colonoscopy↗
PubMed2006

Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients.

BACKGROUND AND AIMS: The incidence of gastric cancer in Japan is four times higher than in the UK. It usually arises in a stomach with corpus predominant or pangastritis that has undergone extensive atrophy and intestinal metaplasia. We hypothesised that a Japanese population would have a more severe gastritis with a corpus predominant or pangastritis pattern and a greater degree of atrophy and intestinal metaplasia than that found in the UK. To test this we designed a comparative trial. METHODS: A total of 252 age matched consecutive patients were recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21 patients were prospectively selected from each decennial, between the ages of 20-80 years. All had epigastric discomfort as their predominant symptom. Patients with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies were examined by two histopathologists using the updated Sydney system. Helicobacter pylori infection was assessed by histology and culture of biopsies and enzyme linked immunosorbent assay and immunoblot of plasma. RESULTS: Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese patients (chi(2) test, p = 0.04). In those patients with gastritis, corpus predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the UK (chi(2) test, p = 0.003) Atrophy and intestinal metaplasia were more extensive and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (chi(2) test, p = 1) Japanese gastritis patients were positive for H pylori. Using a previously described "gastric cancer risk index" among H pylori positive patients, there were significantly more Japanese than UK subjects with a "high risk" score. CONCLUSION: In Japanese as opposed to English patients, gastritis is more prevalent and severe with more corpus predominant atrophy and intestinal metaplasia. These differences may partially explain the higher incidence of gastric cancer in Japan.

Adult↗
PubMed2002

Development of an aggressive depressed cancer in a case of familial adenomatous polyposis.

In 1977, Kariya et al. reported a case of a small depressed cancer in a patient with familial adenomatous polyposis (FAP) raising the possibility that not all cancers in FAP develop from polypoid adenomas. It is now becoming widely recognized that colonic adenomas may appear as flat or depressed lesions. However, colorectal cancers developing in patients with familial adenomatous polyposis (FAP) are still thought to evolve from adenomatous polyps following the polyp-carcinoma sequence. We report the case of a patient with FAP in whom rectal carcinoma developed 23 years after subtotal colectomy and ileorectal anastomosis. We suggest that this malignancy may have developed de novo because of the depressed shape of the lesion and the aggressive growth pattern. This case raises the possibility that carcinomas may not always evolve from polyps in FAP. Aggressive cancers with a depressed appearance should be searched for when surveying the rectal stump in patients with FAP.

Adenocarcinoma↗
PubMed2001

Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor.

Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which are components of a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates a potential high risk for atherosclerosis. In the current study, we show an unexpectedly severe hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-;ob/ob) exhibited striking elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting in extensive atherosclerotic lesions throughout the aorta by 6 months. Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large increase in an apoB-containing broad-beta remnant lipoprotein fraction. While fasting, diet restriction, and low level leptin treatment significantly lowered TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic enzymes suggest that leptin deficiency increased hepatic triglyceride production but did not change cholesterol production in ob/ob mice regardless of their LDLR genotype. These data provide evidence that the hypertriglyceridemia and hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms and point to the possibility that leptin might have some impact on plasma cholesterol metabolism, possibly through an LDLR-independent pathway. This model will be an excellent tool for future studies on the relationship between impaired fuel metabolism, increased plasma remnant lipoproteins, diabetes, and atherosclerosis.

Animals↗
PubMed2001

Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit. Its obligate requirement for the stable expression of oligomeric receptor.

The asialoglycoprotein receptor is an abundant hetero-oligomeric endocytic receptor that is predominantly expressed on the sinusoidal surface of the hepatocytes. A number of physiological and pathophysiological functions have been ascribed to this hepatic lectin (HL), the removal of desialylated serum glycoproteins and apoptotic cells, clearance of lipoproteins, and the sites of entry for hepatotropic viruses. The assembly of two homologous subunits, HL-1 and HL-2, is required to form functional, high affinity receptors on the cell surface. However, the importance of the individual subunits for receptor transport to the cell surface is controversial. We have previously generated HL-2-deficient mice and showed that the expression of HL-1 was significantly reduced, and the functional activity as the asialoglycoprotein receptor was virtually eliminated. However, we failed to detect phenotypic abnormalities. To explore the significance of the major HL-1 subunit for receptor expression and function in vivo, we have disrupted the HL-1 gene in mice. Homozygous HL-1-deficient animals are superficially normal. HL-2 expression in the liver is virtually abrogated, indicating that HL-1 is strictly required for the stable expression of HL-2. Although these mice are almost unable to clear asialo-orosomucoid, a high affinity ligand for asialoglycoprotein receptor, they do not accumulate desialylated glycoproteins or lipoproteins in the plasma.

Animals↗
PubMed2001

Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors.

BACKGROUND: Cyclooxygenase-2 (COX-2) is thought to be linked to carcinogenesis; however, very little is known about its expression in pancreatic neoplasms. The authors studied the expression of COX-2 in human pancreatic neoplasms and investigated the effect of COX inhibitors on the growth of human pancreatic carcinoma cells. METHODS: Expression of COX-2 protein was immunohistochemically examined in 42 human pancreatic duct cell carcinomas (PDCs) and in 29 intraductal papillary mucinous tumors (IPMTs [adenomas, 19; carcinomas, 10]) of the pancreas that were resected surgically at the National Cancer Center Hospital in Tokyo. The growth of four human pancreatic carcinoma cell lines also was evaluated in the presence of COX inhibitors. RESULTS: Marked COX-2 expression was observed in 57% (24 of 42) of PDCs, in 58% (11 of 19) of adenomas, and in 70% (7 of 10) of adenocarcinomas of IPMTs. However, there was no correlation between COX-2 expression and clinicopathologic indices of the patients. All four pancreatic cancer cell lines expressed COX-2 protein weakly or strongly, and the inhibitory effect of aspirin on cell growth was correlated with the expression of COX-2. CONCLUSIONS: COX-2 was expressed in adenomas of IPMTs as well as in carcinomas and might have played a role in the development of pancreatic tumors. In this study, COX inhibitors, as nonsteroidal anti-inflammatory drugs, were shown to be possible preventive agents against pancreatic neoplasms.

Adenocarcinoma, Mucinous↗
PubMed2001

The LDL receptor is the major pathway for beta-VLDL uptake by mouse peritoneal macrophages.

In order to determine the contribution of the low density lipoprotein receptor (LDL-R) to the removal of apoB-containing native lipoproteins by macrophages, we compared the uptake of beta-VLDL in peritoneal macrophages (MPM) from wild type mice and mice lacking the LDL-R. The d<1.006 g/ml lipoproteins obtained from apoE deficient mice fed a high fat diet were poorly degraded by macrophages and caused only a slight formation of CE in macrophages from both types of mice. On the other hand, d<1.006 g/ml lipoproteins obtained from LDL-R deficient mice fed a high fat diet, beta-VLDL with apoE, were avidly taken up by and markedly stimulated CE formation in wild type macrophages, but not in macrophages lacking the LDL-R. The degradation of 125I-labeled-apoE-containing beta-VLDL by wild type MPM was poorly inhibited by unlabeled human LDL, and beta-VLDL without apoE had no effects. In conclusion, we propose that the in vitro uptake of native apoE-enriched lipoproteins by murine macrophages is primarily mediated by the LDL receptor and not by other apoE-recognizing receptor systems such as: the LDL receptor related protein, the VLDL receptor or the triglyceride-rich lipoprotein receptor.

Animals↗
PubMed2001

Evaluation of the necessity for gastrectomy with lymph node dissection for patients with submucosal invasive gastric cancer.

BACKGROUND: When cancer cells are found in the submucosal layer of an endoscopically resected specimen, patients are recommended to undergo gastrectomy with lymph node dissection. If it were possible to identify those patients in whom the risk of lymph node metastasis was negligible, it might be possible to avoid surgery. METHODS: Among those who underwent gastrectomy for gastric cancer from 1980 to 1999, 1091 patients with a cancer invading the submucosa were studied. Clinicopathological factors (sex, age, tumour location, macroscopic type, size, ulceration, histological type, lymphatic-vascular involvement and degree of submucosal penetration) were investigated for their possible association with lymph node metastasis. RESULTS: Lymph node metastases were found in 222 patients (20.3 per cent). Univariate analysis showed that larger tumour size (more than 30 mm), undifferentiated histological type, lymphatic-vascular involvement and massive submucosal penetration had a significant association with lymph node metastasis. Tumour size, histological type and lymphatic-vascular involvement were independent risk factors for lymph node metastasis. By combining these three factors with submucosal penetration of less than 500 microm, 117 patients could be selected as having a minimal risk of lymph node metastasis (95 per cent confidence interval 0-3.1 per cent). CONCLUSION: Lymphadenectomy may not be necessary for patients with gastric cancer invading the submucosa who fulfil the above conditions

Female↗
PubMed2001

Endoscopically demonstrable esophageal changes after Helicobacter pylori eradication in patients with gastric disease.

BACKGROUND AND AIMS: An increased prevalence of reflux esophagitis has been reported following Helicobacter pylori (H. pylori) eradication in patients with duodenal ulcers in Western countries. However, it has remained unknown whether this might also appertain to individuals with other diseases. We therefore carried out this study to determine the effect of eradicating H. pylori infection in a series of Japanese patients. METHODS: Of a total of 203 H. pylori-positive patients successfully cured of infection, 82 cases (58 males, 24 females) with gastric disease, but not duodenal ulcers, were included in the present study; median age 56 years (range 18-80) and median follow up of 24 months (range 6-65). The patients were investigated clinically and endoscopically at regular intervals. RESULTS: Mild reflux esophagitis developed after eradication in three of 55 (5.5%) patients formerly without this condition, while it improved after eradication in five of 27 (18.5%) patients, with the disease endoscopically diagnosed prior to eradication. The estimated incidence of esophagitis within 3 years was 4.8% after cure of infection. Short segment Barrett's esophagus developed after eradication in six of 58 (10.3%) patients who did not have it prior to the therapy, while the condition did not improve in 24 patients affected before eradication. CONCLUSIONS: Endoscopic esophageal changes after H. pylori eradication in the present series of Japanese patients were relatively infrequent and mild. This therapeutic approach thus appears to be safe and unproblematic.

Adolescent↗
PubMed2001

Thiazolidinedione- and tumor necrosis factor alpha-induced downregulation of peroxisome proliferator-activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes.

Thiazolidinediones (TZDs) are antidiabetic insulin-sensitizing agents that bind to peroxisome proliferator-activated receptor gamma (PPARgamma) and have potent adipogenic effects on 3T3-L1 preadipocytes. In fully differentiated 3T3-L1 adipocytes, TZDs markedly decreased PPARgamma mRNA levels without reducing the expression of genes that are positively regulated by PPARgamma, such as adipocyte lipid-binding protein 2 (aP2) or lipoprotein lipase-(LPL). PPARgamma mRNA levels were also downregulated by tumor necrosis factor alpha (TNFalpha), an antiadipogenic cytokine. We propose that the downregulation of PPARgamma is not the common denominator of the metabolic effects of TZDs and TNFalpha on mature adipocytes.

3T3 Cells↗
PubMed2001

Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases.

BACKGROUND AND STUDY AIMS: There have been several published reports on metastatic lesions in the stomach, but the numbers of cases have been limited due to the low frequency of the condition. The present study examined the clinicopathological features of metastatic tumors in the stomach from distant sites in a large series of cases. PATIENTS AND METHODS: A total of 389 patients with gastric metastases from solid malignant tumors were examined between 1968 and 1998 at our institution. Of these, 347 were identified from a series of 6380 autopsy cases; 54 patients were diagnosed endoscopically while alive, 12 of whom had confirmation of the condition at autopsy. RESULTS: In the endoscopically diagnosed cases, the metastases presented as solitary (65%) or multiple lesions (35 %), and were more frequently located in the middle or upper third of the stomach. Although the endoscopic appearance often resembled that of submucosal tumor (51%) or primary gastric cancer (39%), the final diagnosis was easily obtained in over 90% of cases from endoscopic biopsies. In two cases of lung cancer and breast cancer, gastric metastases were found before the primary tumors. In the autopsy cases with solid malignancies, metastatic lesions to the stomach were found in 5.4%, and the lung, breast, and esophagus were common primary sites. Malignant melanoma was the most frequent tumor to metastasize to the stomach (29.6%). CONCLUSIONS: Since metastatic lesions to the stomach are rare, the above characteristics of the lesions should be borne in mind, and biopsies should be taken for precise diagnosis during endoscopic examinations.

Adult↗
PubMed2001

Endoscopic mucosal resection.

We are now finding more malignancies in their early stages than previously. Attempts to ablate these lesions are difficult and do not provide the histological information required to decide on further treatment. Surgery is difficult to justify, as only a minority of lesions are associated with lymph node metastases and lesions may not become clinically relevant within the lifetime of an elderly patient. Endoscopic mucosal resection allows cancers to be resected at minimal cost, morbidity and mortality. It is also the most reliable investigation when assessing lesions which are suspicious for containing early cancer. After endoscopic removal, histological assessment of depth of penetration and a search for invasion into lymphatics or venules allows the risk of microscopic lymph node metastases to be predicted. The risk of developing metastatic disease can then be balanced against the risks of surgery in view of the patient's age and health.

Biopsy↗
PubMed2001

Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy.

BACKGROUND: Mucosal iodine staining is known to improve the endoscopic visualization of esophageal squamous dysplasia and cancer. However, it often causes mucosal irritation leading to retrosternal discomfort. The clinical usefulness of sodium thiosulfate solution (STS) for easing symptoms induced by mucosal staining with Lugol's solution was evaluated in this study. METHODS: One hundred twenty healthy men over 50 years of age were enrolled in the study. They each underwent esophagogastroscopy including the spraying of Lugol's iodine solution (10 mL) on the mid and distal esophagus and were subsequently randomized into three groups: (I) no treatment (n = 40), (II) spraying of 20 mL of aluminum-magnesium hydroxide gel (Maalox) by means of endoscopic catheter (n = 40), and (III) spraying of 20 mL of 5% sodium thiosulfate solution by means of endoscopic catheter (n = 40). An hour after the endoscopic examination the subjects were asked to complete a questionnaire that addressed adverse symptoms induced by Lugol's iodine staining. RESULTS: Sodium thiosulfate solution spray substantially reduced adverse symptoms that lasted more than 30 minutes after chromoendoscopy, compared with the no-treatment group. There was no significant difference in the proportion of subjects with symptoms between the Maalox and no-treatment groups. Cost of sodium thiosulfate solution spray per use was $0.15 (15 yen). CONCLUSIONS: Sodium thiosulfate solution is recommended for routine use after Lugol's staining.

Coloring Agents↗
PubMed2001

Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter.

In an attempt to identify transcription factors which activate sterol-regulatory element-binding protein 1c (SREBP-1c) transcription, we screened an expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse SREBP-1 gene promoter. We cloned and identified the oxysterol receptors liver X receptor (LXRalpha) and LXRbeta as strong activators of the mouse SREBP-1c promoter. In the transfection studies, expression of either LXRalpha or -beta activated the SREBP-1c promoter-luciferase gene in a dose-dependent manner. Deletion and mutation studies, as well as gel mobility shift assays, located an LXR response element complex consisting of two new LXR-binding motifs which showed high similarity to an LXR response element recently found in the ABC1 gene promoter, a reverse cholesterol transporter. Addition of an LXR ligand, 22(R)-hydroxycholesterol, increased the promoter activity. Coexpression of retinoid X receptor (RXR), a heterodimeric partner, and its ligand 9-cis-retinoic acid also synergistically activated the SREBP-1c promoter. In HepG2 cells, SREBP-1c mRNA and precursor protein levels were induced by treatment with 22(R)-hydroxycholesterol and 9-cis-retinoic acid, confirming that endogenous LXR-RXR activation can induce endogenous SREBP-1c expression. The activation of SREBP-1c by LXR is associated with a slight increase in nuclear SREBP-1c, resulting in activation of the gene for fatty acid synthase, one of its downstream genes, as measured by the luciferase assay. These data demonstrate that LXR-RXR can modify the expression of genes for lipogenic enzymes by regulating SREBP-1c expression, providing a novel link between fatty acid and cholesterol metabolism.

Alitretinoin↗