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Biomedical subjects

N Yahagi

Publications and source records attributed to N Yahagi.

At least 19 recordsLinked to original sources

The useful combination of a higher frequency miniprobe and endoscopic submucosal dissection for the treatment of T1 esophageal cancer.

BACKGROUND: There are few published data on the discrimination ability of endoscopic ultrasonography (EUS) among each subdivision of T1 cancer, and overdiagnosis is an unsolved problem that eventually causes overtreatment. The purpose of this study was to verify whether our treatment strategy incorporating EUS realizes a tailored patient management of T1 esophageal cancer. METHODS: This study comprised 20 esophageal cancer patients undergoing 12- to 20-MHz miniprobes for T staging and a 7.5-MHz dedicated echoendoscope for N staging. Initial therapy constituted endoscopic submucosal dissection (ESD) for endosonographically node-negative, mucosal, or slight submucosal cancers and a primary esophagectomy with three-field lymphadenectomy for deeper cancers. If the ESD specimen revealed no cancer involvement of the muscularis mucosa, the patients entered a follow-up program; otherwise, they were advised to undergo a subsequent esophagectomy and three-field lymphadenectomy. RESULTS: Perfect discrimination accuracy was achieved among T1, T2, and T3 cancers. Whether cancer depth was up to the slight submucosal layer or deeper was correctly differentiated in 12 of 14 T1 cancers (86%). EUS categorized all patients correctly into candidates for either ESD or surgery. The pathological cancer depth of the resected specimens revealed that no patients experienced unnecessary overtreatment. CONCLUSIONS: A higher frequency miniprobe is useful for the detailed evaluation of cancer depth, contributing to decision making for treatment options of T1 esophageal cancer. A miniprobe and echoendoscope in combination with ESD provide an appropriately tailored management plan on an individual basis, avoiding unnecessary treatment or indicating radical surgery.

Adenocarcinoma↗

Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction.

BACKGROUND AND STUDY AIMS: The esophagogastric junction (EGJ) has been considered a difficult location for endoscopic treatment of tumors, due to its narrow lumen and sharp angle. Endoscopic submucosal dissection (ESD) is a method of endoscopic resection, capable of removing large tumors in an en bloc fashion. The aim of this study was to evaluate the efficacy and safety of ESD for EGJ tumors. PATIENTS AND METHODS: For 30 lesions of EGJ tumors treated by ESD, the size of the lesions and resected specimens, the en bloc resection rate, complications, and local recurrence were assessed. RESULTS: The average maximum diameters of the lesions and resected specimens were 22.4 mm and 40.6 mm respectively. The complete en bloc resection (R0) rate was 97% (29/30). Histological evaluation of the resected specimens revealed five cases of angiolymphatic invasion and five cases of submucosal invasion deeper than 500 microm. Perforation occurred in one case but was safely managed by rotatable clips and administration of antibiotics for 3 days. Local recurrence was not observed in any patient during follow-up (mean 14.6 months, range 6-31 months). CONCLUSIONS: ESD can be safely performed for EGJ tumors, with a high en bloc resection rate. For lesions with no apparent submucosal invasion findings, ESD is a curative and diagnostic treatment option that may be considered before open surgery.

Adenocarcinoma↗

Histopathologic characteristics of gastric ulcers created by endoscopic submucosal dissection.

BACKGROUND AND STUDY AIM: We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. PATIENTS AND METHODS: 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. RESULTS: Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. CONCLUSION: Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.

Aged↗

Endoscopic submucosal dissection for rectal epithelial neoplasia.

BACKGROUND AND STUDY AIMS: The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients' quality of life, it may be desirable to use the same technique for rectal neoplasia. PATIENTS AND METHODS: Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. RESULTS: The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. CONCLUSIONS: ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.

Chi-Square Distribution↗

Successful nonsurgical management of perforation complicating endoscopic submucosal dissection of gastrointestinal epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. PATIENTS AND METHODS: We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. RESULTS: Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). CONCLUSION: Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Aged↗

Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer.

The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.

Adult↗

Epidemiological and outcome characteristics of major burns in Tokyo.

The Tokyo Burn Unit Association (TBUA) was established in 1983 funded by the Tokyo Metropolitan Government, and is organized by 13 burn units in Tokyo. TBUA covers more than 90% of severe burn patients occurring in Tokyo, and all of the cases are registered according to the burn injury registration format. The purpose of this study is to analyze the registered data and to elucidate epidemiological and outcome characteristics of major burn injuries in Tokyo. The total of 6988 hospitalized patients had data for epidemiological analysis, and 6401 patients had complete data for outcome analysis as well, and were included in this study. The characteristic profiles for the analysis included age, sex, cause of burns, inhalation injury, %BSA, burn index (BI), length of burn unit stay, and outcome, and were analyzed by age groups. The mean age of the patients was 40.4 years, and 63% of them were male. It was noteworthy that 25% of the total patients were elderly patients over 60 years of age. Flame was the most common cause making up 45.6% followed by scalding (32.0%). The overall mortality rate was 15.4%. Inhalation injury was accompanied in 27.3% of burn patients. The mortality rate was 34.6% with inhalation injury, and 8.2% without inhalation injury. Causes of death showed that multiple organ failure made up 36.9% of total mortality, followed by sepsis 25.2 and shock 19.0%. The burn size (%BSA and BI) and inhalation injury were the factors for high mortality rate in all age groups whereas age was a predictor for high mortality in the patients older than 16 years of age. Gender was not a factor for high mortality in any age group. The mortality rate showed mildly decreasing tendency since 1995 for which implementation of skin bank was thought to be responsible.

Adolescent↗

Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: One of the major complications of endoscopic mucosal resection (EMR) for gastrointestinal tumors is perforation, and the most effective way of preventing perforation is to elevate the lesion sufficiently by endoscopic injection of fluid into the submucosa. MATERIALS AND METHODS: In order to compare the lesion-lifting properties of several different solutions, 1 ml of each of the following solutions was injected into the submucosa of the resected porcine stomach: normal saline, 3.75 % NaCl, 20 % dextrose water, 10 % glycerin with 0.9 % NaCl plus 5 % fructose, and two sodium hyaluronate (SH) solutions. RESULTS: Significantly higher initial elevation was produced by both SH solutions, and it remained higher than that achieved by the other solutions at all times. Hypertonic solutions, especially 10 % glycerin with 0.9 % NaCl plus 5 % fructose, tended to produce and maintain greater mucosal elevation than normal saline, but the difference was not significant. CONCLUSIONS: SH solutions were the most suitable ones for producing and maintaining long-term mucosal elevation, while the superiority of hypertonic solutions over normal saline was not clearly demonstrated.

Animals↗

Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Sodium hyaluronate (SH) is a promising submucosal injection solution during endoscopic mucosal resection, but its high cost is an obstacle to more widespread use. The aim of this study was to identify an appropriate low-cost SH solution by varying the molecular weight of SH and mixing various solutions with it. MATERIALS AND METHODS: The viscoelasticity of various SH solutions was first measured. The concentrations of two 1 % SH preparations with different molecular weights (800 kDa and 1900 kDa) were adjusted to 0.5 %, 0.25 %, and 0.125 %, using 0.9 %/3.75 % normal saline (NS), 5 %/20 % dextrose water (DW), and a glycerin solution (Glyceol): 10 % glycerin with 0.9 % normal saline plus 5 % fructose. The ability of these SH solutions to create submucosal fluid cushions (SFCs) was then investigated in the stomachs of two live minipigs. RESULTS: The 0.25 % 1900 kDa SH/NS solution and the 0.125 % 1900 kDa SH/20 % DW solution created a similar viscoelasticity to that of the 0.5 % 800 kDa SH/NS solution. The ability of these solutions to create SFCs was also similar. In addition, the 0.125 % 1900 kDa SH/Glyceol solution created similar SFCs, with a synergistic effect of increased viscoelasticity and the hypertonic nature of glycerin. CONCLUSIONS: A mixture of higher molecular weight sodium hyaluronate with a sugar solution (particularly 20 % dextrose), with or without glycerin, should be regarded as a cost-effective option for creating SFCs instead of the conventional SH solution made with the same amount of a 1 % 800 kDa SH preparation and normal saline.

Animals↗

Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach.

The oncogene function in primary epithelial cells is largely unclear. Recombination organ cultures in combination with the stable and transient gene transfer techniques by retrovirus and electroporation, respectively, enable us to transfer oncogenes specifically into primary epithelial cells of the developing avian glandular stomach (proventriculus). In this system, the epithelium and mesenchyme are mutually dependent on each other for their growth and differentiation. We report here that either stable or transient expression of v-src in the epithelium causes budding and migration of epithelial cells into mesenchyme. In response to the transient expression of v-Src or a constitutive active mutant of MEK, we observed immediate downregulation of the Sonic hedgehog gene and subsequent elimination of E-cadherine expression in migrating cells, suggesting the involvement of MAP kinase signaling pathway in these processes. v-src-expressing cells that were retained in the epithelium underwent apoptosis (anoikis) and detached from the culture. Continuous expression of v-src by, for example, Rous sarcoma virus (RSV) was required for the epithelial cells to acquire the ability to express type I collagen and fibronectin genes (mesenchymal markers), and finally to establish the epithelial-mesenchymal transition. These observations would partly explain why RSV does not apparently cause carcinoma formation, but induces sarcomas exclusively.

Animals↗

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↗

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↗

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↗

Causes of airway obstruction during cuffed oropharyngeal airway use.

This study investigated the cause for needing airway maneuvers to maintain a patent airway during the use of cuffed oropharyngeal airway (COPA). Twenty adult patients (29.4+/-6.8 years-old, ASA 1-2) scheduled for minor gynecological surgery who required brief manipulations of the airway despite COPA use following the manufacture's guidelines, were enrolled in this study. To obtain airway patency, 15 patients required only the head-tilt maneuver. In eight of the 15 patients, the laryngeal inlet was opened partially (n=4) or completely (n=4). Despite lifting the epiglottis, the laryngeal inlet was incomplete at the level of pharyngeal view. The patency of the laryngeal inlet was decided by the extent of the distance between the posterior pharyngeal wall and the lateral glossoepiglottic fold, which was made by hyoid bone. In the other seven patients, the head-tilt maneuver elevated the epiglottis and completely opened the laryngeal inlet. Five patients required both the jaw-thrust and head-tilt maneuver. Of these patients lifting the epiglottis was incomplete in three and the laryngeal inlet was partially collapsed in one even after the airway manipulations. The airways in these three patients, however, became patent after manipulations despite the persisting partial obstruction.

Adult↗