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Biomedical subjects

Naohisa Yahagi

Publications and source records attributed to Naohisa Yahagi.

At least 19 recordsLinked to original sources
PubMed2007

[Endoscopic resection for early gastric cancers by EMR/ESD].

The key issue in the field of therapeutic endoscopy in recent years is the development of a new therapeutic strategy for early gastric cancers using endoscopic submucosal dissection (ESD) technique. ESD was developed to overcome the problem of remnant or recurrent tumors after incomplete resection by conventional endscopic mucosal resection (EMR). Ever since after the emergence of ESD, indication criteria for endoscopic resection of early gastric cancers were extended through expansion of both theoretical and technical conditions. Complete en bloc resection rates were 96.7% and 62.6% in the ESD group and the EMR group, respectively, in our institution. ESD is a highly effective technique enabling us to resect much larger and difficult lesions, which cannot be resected by conventional EMR techniques. However, it involves a much higher complication rate and requires much higher skills. A small lesion less than 20 mm located in a good position can be resected completely, without any difficulties using conventional EMR techniques. Therefore, we must consider the approach to treatment, when conducting an endoscopic resection,it terms of the situation and skills of the endoscopist.

Digestive System Surgical Procedures↗
PubMed2006

Endoscopic submucosal dissection of esophageal squamous cell neoplasms.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) has recently been developed for en bloc resection of stomach neoplasms, which results in high tumor eradication rates as well as a modality for the precise histologic assessment of the entire lesion. Application of the technique is desirable for esophageal squamous cell neoplasms (SCNs), but there have been no reports on the use of this procedure in the esophagus. METHODS: An ESD with methods similar to those used for resections of early gastric cancer was performed on 58 consecutive esophageal SCNs with preoperative diagnoses of intraepithelial neoplasm or intramucosal invasive carcinoma occurring in 43 enrolled patients. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The rate of en bloc resection was 100% (58/58), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 78% (45/58). There was no evidence of significant bleeding. Perforation occurred in 4 (6.9%) patients during the ESD, who were managed by conservative medical treatments after endoscopic closure of the perforation. Removal of 9 (16%) lesions resulted in esophageal stricture requiring balloon dilation after ESD. Of 40 lesions occurring in 31 patients fulfilling the criteria of node-negative tumors (mean follow-up, 17 months), 1 lesion resected by en bloc resection with nonevaluable tumor-free lateral margins (Rx [lateral] resection) recurred locally 6 months after ESD, which was treated successfully by a second ESD procedure. CONCLUSIONS: The ESD is applicable to the esophagus with promising results, but notification of risk is essential.

Coloring Agents↗
PubMed2006

Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar.

BACKGROUND: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation is to create a sufficient submucosal fluid cushion (SFC). The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol). METHODS: Sixty-seven consecutive GI tumors in 54 patients who met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1:3 for esophageal/colorectal tumors and stomach tumors with scar, and 1:7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. The clinical outcomes were investigated. RESULTS: Mean resected and tumor sizes were 38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with severe fibrosis (1.5%), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. In one stomach and in one rectal tumor (3%), endoscopic hemostasis was necessary because of postoperative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow-up of 1 year. CONCLUSIONS: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD.

Adjuvants, Immunologic↗
PubMed2006

Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection.

Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR.

Animals↗
PubMed2006

En bloc resection of a large semicircular esophageal cancer by endoscopic submucosal dissection.

A semicircular esophageal cancer, approximately 7 cm wide, was detected in the middle to lower esophagus of an 81-year-old gentleman during an esophagogastroduodenoscopy. Thorough examinations using chromoendoscopy and endoscopic ultrasonography led to preoperative diagnosis of an intramucosal tumor. With informed consent, the patient underwent endoscopic submucosal dissection (ESD), a novel endoscopic treatment. A successful en bloc resection by ESD was completed without complications. The resected specimen measured 72 mm by 35 mm, and the cancer was contained in an area of 66 mm by 32 mm. Histologic assessment revealed squamous cell carcinoma, microinvasive into the mucosal layer, but without vessel infiltration. Six months after ESD, mild stenosis remained, but dilation was no longer needed, and esophagogastroduodenoscopy with chromoendoscopy and biopsy revealed no residual or recurrent cancer.

Aged, 80 and over↗
PubMed2006

Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma.

The authors investigated whether high-dose methotrexate-induced toxicity differed according to the presence of methylenetetrahydrofolate reductase (MTHFR) or reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15 children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were treated using protocols that included high-dose methotrexate (3.0 g/m), for an overall total of 43 courses. Methotrexate-induced toxicities and the plasma methotrexate concentrations were evaluated retrospectively. Hematologic toxicity was the most frequently observed toxicity, appearing in 87% of the patients. In a subset of patients (47%), elevation of liver transaminase levels showed a repeated tendency to develop. High plasma methotrexate concentrations at 48 hours after the methotrexate infusion were not significantly related to methotrexate-induced toxicities except for mucositis. A generalized estimating equation analysis revealed that vomiting during the high-dose methotrexate treatment was more pronounced in patients who had a larger number of G alleles at the RFC1 80G>A polymorphism. No significant differences in the development of other toxicities or in the plasma methotrexate concentrations were observed for the different MTHFR 677C>T or RFC1 80G>A polymorphisms. This study suggests but does not prove that the RFC1 80G>A polymorphism may contribute to interindividual variability in responses to high-dose methotrexate.

Adolescent↗
PubMed2006

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Animals↗
PubMed2006

Helicobacter pylori status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal dissection.

BACKGROUND: Eradication therapy for Helicobacter pylori is effective in preventing peptic ulcer recurrence, but its efficacy in ulcer healing is still controversial. The effect of H. pylori on artificial ulcers after endoscopic resection is not known. The purpose of the present study was therefore to evaluate the influence of H. pylori infection on ulcer healing after endoscopic submucosal dissection (ESD). METHODS: One hundred and 10 patients who underwent ESD for gastric tumors, and for whom the infection status of H. pylori was confirmed before treatment, were included. The healing stage was studied by endoscopy performed at 8 weeks after ESD. In addition, 73 patients whose serum pepsinogen (PG) was evaluated before ESD, were divided into three groups: PG positive (PGI<or=70 ng/mL and I/II<or=3 ng/mL), strongly positive (PGI<or=30 ng/mL and I/II<or=2 ng/mL) and negative, to study the influence of atrophic gastritis on ulcer healing. RESULTS: Ulcer healing was observed in 85 patients (93%) who were H. pylori positive, and in 19 patients (100%) in whom H. pylori had been eradicated previously. Serum PG level had no influence on the healing process. Among 15 patients with ulceration or ulcer scar with the lesion, ulcer healing was observed in nine patients (60%), which was significantly low. CONCLUSIONS: Infection status of H. pylori and the extent of gastric atrophy do not affect ulcer healing after ESD. Preoperative existence of fibrotic change in the submucosal layer may delay the healing process.

Female↗
PubMed2006

[A case of gastric cancer presenting with obstructive jaundice and responding to biweekly CPT-11 and CDDP combination administration].

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.

Adenocarcinoma, Mucinous↗
PubMed2005

The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.

Use of herbal remedies in the treatment of various diseases has a long tradition in Eastern medicine and the liver diseases are not an exception. In their use, lack of elucidation of mechanism(s) as well as randomized, placebo-controlled clinical trials has been a problem. Recently, we and others reported that inchin-ko-to (TJ-135), one of herbal remedies, suppressed hepatic fibrosis in animal models. In the course of clarifying the mechanism, we directed our focus on hepatic stellate cells (HSCs), playing a pivotal role in hepatic fibrosis, and found that rat HSCs cultured with TJ-135 changed their morphology to star-like configuration with thin, slender and dendritic processes with fewer stress fibers, which might be the features in apoptosis. In fact, TJ-135 induced HSC apoptosis in a time- and concentration-dependent manner as judged by the nuclear morphology, quantitation of cytoplasmic histone-associated DNA oligonucleosome fragments and caspase 3 activity. In HSCs treated with TJ-135, increased expression of p53 and decreased expression of Bcl-2 and phosphorylated Akt and Bad were determined. HSC apoptosis is shown to be involved in the mechanisms of spontaneous resolution of rat hepatic fibrosis and the agent which induces HSC apoptosis has been shown to reduce experimental hepatic fibrosis in rats. Thus, the induction of HSC apoptosis could be the mechanism how TJ-135 works on the resolution of hepatic fibrosis. Our current data may shed light on the novel effect of the herbal remedy.

Animals↗
PubMed2005

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential.

The mammalian SWI/SNF chromatin remodeling complex is composed of more than 10 protein subunits, and plays important roles in epigenetic regulation. Each complex includes a single BRG1 or Brm molecule as the catalytic subunit. We previously reported that loss of Brm, but not BRG1, causes transcriptional gene silencing of murine leukemia virus-based retrovirus vectors. To understand the biological function and biogenesis of Brm protein, we examined seven cell lines derived from various human tumors that do not produce Brm protein. We show here that these Brm-deficient cell lines transcribe the Brm genes efficiently as detected by nuclear run-on transcription assay, whereas Brm mRNA and Brm hnRNA were undetectable by reverse transcription-polymerase chain reaction analysis. These results indicate that expression of Brm is strongly and promptly suppressed at the post-transcriptional level, through processing and transport of the primary transcript or through stability of mature Brm mRNA. This suppression was attenuated by transient treatment of these cell lines with HDAC inhibitors probably through indirect mechanism. Importantly, all of the treated cells showed prolonged induction of Brm expression after the removal of HDAC inhibitors, and acquired the ability to maintain retroviral gene expression. These results indicate that these Brm-deficient human tumor cell lines carry a functional Brm gene. Treatment with HDAC inhibitors or introduction of exogenous Brm into Brm-deficient cell lines significantly reduced the oncogenic potential as assessed by colony-forming activity in soft agar or invasion into collagen gel, indicating that, like BRG1, Brm is involved in tumor suppression.

Blotting, Western↗
PubMed2005

Tissue damage of different submucosal injection solutions for EMR.

BACKGROUND: When choosing submucosal injection solutions for EMR, tissue damage should be considered, as well as the lesion-lifting ability. The objective of the study was to find out the potential tissue damage of submucosal injection solutions. METHODS: The submucosal injection solutions examined were the following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5% fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and 0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable concentration without tissue damage. A total of 2 mL of each solution per stomach were injected by endoscopy into the submucosal layer at the separate sites of 4 living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic observations, and the others were euthanized after additional endoscopic observations a week after injection. RESULTS: There was no apparent tissue damage in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic solutions, except Glyceol and 10% DW, have more or less potency of tissue damage. In 3.75% NaCl and DW with concentrations of >or=20%, considerable tissue damage was observed, which might affect resected EMR specimens and ulcer healing. CONCLUSIONS: Use of hypertonic solutions except Glyceol is not recommended with respect to tissue damage. A combination of HA and Glyceol is the most favorable submucosal injection solution, considering tissue damage and lesion-lifting ability.

Animals↗
PubMed2005

Pancreas duct abnormalities in patients with ulcerative colitis: a magnetic resonance pancreatography study.

BACKGROUND: The presumed etiology and prevalence of pancreatic abnormalities in patients with ulcerative colitis (UC) have been controversial. We conducted a controlled (cross-sectional) study of patients with UC compared with non-UC controls to determine the prevalence of pancreatic duct abnormalities in patients with UC and to determine if these are specific to UC using magnetic resonance cholangiopancreatography. METHODS: Magnetic resonance cholangiopancreatography was performed on 79 unselected patients with UC and 45 non-UC controls, without a history of pancreatitis attack, between February 2000 and May 2003. RESULTS: Among patients with UC, the prevalence of pancreatic duct abnormalities was 16.4% (95% confidence interval, 8.3%-24.6%): coexisting dilatation and narrowing of the main pancreatic duct were found in 5; diffuse narrowing of pancreatic ducts in 5; and dilatation of pancreatic ductal branches in 3. These abnormalities were compatible with chronic pancreatitis. Among the controls, no pancreatic duct abnormality was found. CONCLUSIONS: Changes in the pancreatic duct were found in approximately one-sixth of patients with UC, none of whom had a history of overt pancreatitis. These pancreatic duct abnormalities are likely to be specific to patients with UC.

Adolescent↗
PubMed2005

Endothelin-3 controls growth of colonic epithelial cells by mediating epithelial-mesenchymal interaction.

It has been repeatedly reported that endothelin-3 (ET-3) is expressed by gastrointestinal mesenchymes, and that paracrine signaling between ET-3 and its receptor plays an essential role in controlling differentiation of the enteric nervous system in the gut, especially in the colon. However it remains to be solved whether ET-3 plays a role in regulating the growth of gastrointestinal epithelial cells. We have previously reported culture systems for forestomach, glandular stomach and duodenal epithelial cells, but a system for colonic epithelial cells has not been established. In the present study, we examined optimal culture conditions for colonic epithelial cells, and examined whether ET-3 affects the growth of gastrointestinal epithelial cells, with special reference to colonic cells. We found that ET-3 dose-dependently and region-specifically stimulated their growth in primary culture: colonic epithelial cells were most responsive, followed by duodenal and glandular stomach epithelial cells. Reverse transcription-polymerase chain reaction analysis showed that ET-3 and a receptor for ET-3 were expressed by both colonic mesenchymes and epithelia, but the levels were much higher in mesenchymes than in epithelia. These results suggest that ET-3 plays an important role in the growth control of colonic epithelial cells, possibly by mediating epithelial-mesenchymal interactions.

Animals↗