Fuminao Takeshima

Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma

BACKGROUND Endoscopic submucosal dissection (ESD) permits en bloc removal of superficial esophageal squamous cell carcinoma. However, postprocedure stricture is common after ESD for extensive tumors, and multiple endoscopic balloon dilation (EBD) is required for recalcitrant cases. OBJECTIVE To evaluate the effectiveness of oral prednisolone in controlling postprocedure esophageal stricture. DESIGN Retrospective study. SETTING Endoscopy department at a university hospital. PATIENTS Patients who underwent complete circular or semicircular ESD for esophageal squamous cell carcinoma involving more than three fourths of the lumen were treated with either pre-emptive EBD or oral prednisolone. INTERVENTION Preemptive EBD was started on the third day post-ESD and continued twice weekly for 8 weeks. Oral prednisolone was started at 30 mg/day on the third day post-ESD , tapered gradually, and then discontinued 8 weeks later. An additional EBD was performed on demand in both groups whenever dysphagia appeared. MAIN OUTCOME MEASUREMENT The incidence of esophageal stricture and number of EBD sessions required to relieve dysphagia. RESULTS Stricture at 3 months after ESD was found in 7 of 22 patients in the preemptive EBD group but only 1 of 19 in the oral prednisolone group (P < .05). The average number of EBD sessions required was 15.6 in the preemptive EBD group and 1.7 in the oral prednisolone group (P < .0001). After complete circular ESD, 32.7 EBD sessions were needed on average in the preemptive EBD group, whereas fewer were needed in the oral prednisolone group (P < .05). LIMITATIONS Nonrandomized study. CONCLUSIONS Post-ESD esophageal strictures were persistent even if treated preemptively with multiple EBD sessions, but oral prednisolone may offer a useful preventive option.

Peroral endoscopic myotomy for esophageal achalasia: Clinical impact of 28 cases

The aim of the present study was to clarify the efficacy of peroral endoscopic myotomy (POEM) for esophageal achalasia.

Enhanced Expression of Interleukin-8 and Activation of Nuclear Factor Kappa-B in Endoscopy-negative Gastroesophageal Reflux Disease

OBJECTIVE:Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-κB) activation, which upregulates IL-8 expression.METHODS:We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-κB-DNA binding assay and immunohistochemical analyses of NF-κB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1.RESULTS:The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-κB activation in esophageal mucosa in GERD patients and the NF-κB subunits were localized predominantly in the nuclei of IL-8-expressing cells.CONCLUSIONS:Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-κB activation may be implicated in the pathogenesis in GERD.

Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma

BackgroundEndoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms en bloc, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD.MethodsSeven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia.ResultsEn bloc ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions.ConclusionsUse of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.

Implication of NF-kappaB in Helicobacter pylori-associated gastritis

OBJECTIVE:Transcription factor NF-κB plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-κB in Helicobacter pylori–associated gastritis (HAG).METHODS:We examined 41 patients with HAG and 18 H. pylori–negative control subjects. Expression of activated NF-κB was studied in situ by immunohistochemistry using α-p65 mouse monoclonal antibody (α-p65 mAb), which recognizes activated NF-κB. To identify the cell types in which NF-κB was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-κB with the expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-κB–dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1α (MIP-1α) in antral mucosa by ELISA (ELISA).RESULTS:Activated NF-κB was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-κB positivity index (NF-κB PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-κB, was significantly higher in patients with HAG than in H. pylori–negative controls. NF-κB PI correlated significantly with histological scores of gastritis. Moreover, activated NF-κB was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-κB with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-κB PI.CONCLUSIONS:In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-κB. In these cells, activated NF-κB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.

Magnifying Endoscopic Findings Can Predict Clinical Outcome during Long-Term Follow-Up of More Than 12 Months in Patients with Ulcerative Colitis

Background and Aims. To explore the association of magnifying endoscopic (ME) findings with histopathology and relapse in ulcerative colitis (UC). Methods. Forty-six patients with UC underwent ME with narrow band imaging (NBI) and crystal violet staining and were followed for more than 12 months. ME findings with vital staining were classified into ME-A, regular arrangement of round to oval pits; ME-B, irregular arrangement with/without enlarged spaces between even pits; ME-C, irregular pits in size and shape with more irregular arrangement of pits; and ME-D, disrupted or disappeared pits. NBI-guided ME features of microvascular pattern (MVP) were divided into the MVP-regular and MVP-irregular type. Results. There were 5, 24, 10, and 7 cases of ME-A, ME-B, ME-C, and ME-D grade, respectively, while there were 21 and 25 of MVP-regular and MVP-irregular type, respectively. ME classifications were significantly associated with Matts endoscopic grade. ME classifications and MVP types were significantly associated with each pathognomonic microscopic feature of severe mucosal inflammation, crypt abscess, and goblet cell depletion. There were significant differences in the percentages of remission among ME classifications and between MVP types. Conclusion. ME findings can be predictive of relapse in UC and reliable for in vivo histopathological assessment.

Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer

Heat shock proteins (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. We determined the expression of Hsp 70 and Hsp 40 in 81 gastric cancers. Immunoreactivities to Hsp 70 and Hsp 40 were detected in 67.9 and 22.2% of tumors, respectively. Immunohistochemical analysis showed enhanced Hsp 70 and Hsp 40 expression in gastric tumor tissue, relative to the surrounding normal tissue. Overexpression of Hsp 70 and Hsp 40 was also confirmed by immunoblotting. Among various clinicopathological parameters, low histopathological differentiation was associated with reduced expression of both proteins.

Recent insights into digestive motility in functional dyspepsia

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.

Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia.

Background and Goals Neurohormonal factors might play a role in the pathogenesis of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal hormone that stimulates gastric motility, in FD is not yet clearly defined. The present study was designed to investigate plasma ghrelin levels and their relation with gastric emptying and psychologic status in FD. Methods Sixteen patients with FD of the dysmotility type and 19 healthy controls were enrolled in the study. Plasma active and desacyl ghrelin concentrations before and after test meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and psychologic condition were studied using 13C acetate breath test and questionnaires, respectively. Results Gastric emptying was significantly prolonged in patients with FD compared with controls. Fasting desacyl and total ghrelin levels were significantly lower in FD patients than in controls, but fasting active ghrelin levels and postprandial levels of ghrelin in both forms were similar between the 2 groups. Fasting total ghrelin levels in FD patients did not differ from the postprandial levels, in contrast to what was found for controls. There was no significant association among gastric emptying, plasma ghrelin levels, and psychologic factors in FD patients. Conclusions Total secretory ability or metabolic condition of ghrelin may be altered in patients with FD. This seems to play a role in the pathophysiology of dysmotility type FD, independent of delayed gastric emptying or psychologic disorders.

Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma

Background:  The long‐term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor‐related variables and liver function.