Naoyuki Yamaguchi

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.

Clinicopathological factors associated with clinical outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) permits removal of colorectal epithelial neoplasms en bloc, but a substantial risk of procedure-related perforation has been reported. We sought to unravel the clinicopathological factors associated with the clinical outcomes of ESD for colorectal epithelial neoplasms in a large series. PATIENTS AND METHODS ESD was done in 278 patients with 292 colorectal tumors that fulfilled the inclusion criteria. The criteria for ESD were: lesion greater than 20 mm in size, lesion with fibrotic scarring, locally residual colorectal lesion, or invasive carcinoma with slight submucosal penetration. Resection was assessed as en bloc or piecemeal, complete (en bloc with tumor-free lateral and basal margins) or incomplete. Complications including perforation and bleeding were assessed, and factors related to each were analyzed using logistic regression. Patients underwent multiple follow-up endoscopic examinations (mean 4.6; median 4; range 2 - 9; total number 1010). RESULTS En bloc resection was achieved in 90.1 % of lesions (263/292) and resection was deemed to be complete in 233 (79.8 %). Right-side colonic location and the finding of fibrosis were the significant contributors to incomplete resection. Perforation was seen in 24 cases (8.2 %), and was associated with large tumor size and the presence of fibrosis. When the contributive factors for each were combined, the risks of incomplete resection and perforation were substantially increased. CONCLUSION The present study provides useful information for predicting risks for incomplete resection and complication in colorectal ESD.

MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC.MethodsTotal RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR.ResultsBased on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC.ConclusionsThese results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer by indication criteria.

Background and Study Aims: Endoscopic submucosal dissection (ESD) can remove early gastric cancer (EGC) en bloc. We sought to assess the feasibility and efficacy of ESD and the clinical outcomes based on the indication criteria. Patients and Methods: 551 patients with 589 EGC lesions were divided into the guideline criteria group (elevated lesion ≤20 mm in diameter and depressed lesion ≤10 mm without ulceration) and the expanded criteria group (mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings ≤3 cm in diameter; and minute submucosal invasive cancer ≤3 cm in size). Results: En bloc, complete and curative resection were achieved in 98.6 and 93.0, 95.1 and 88.5, and 97.1 and 91.1%, for the guideline and expanded criteria lesions, respectively; the differences between the 2 groups were significant for each. The expanded criteria lesions were at significantly higher risk of ESD-associated bleeding and perforation. Overall survival was adequate irrespective of the indications, and the disease-specific survival rates were 100% in both. Conclusion: ESD for EGCs that met the expanded criteria was acceptable, though the resection rates and safety were decreased compared to those for the guideline criteria lesions.

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.

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.

Clinical outcomes of endoscopic submucosal dissection in elderly patients with early gastric cancer.

Objectives Endoscopic submucosal dissection (ESD) has advantages over conventional endoscopic mucosa resection. The number of elderly patients (more than 75 years old) with early gastric cancer (EGC) has been steadily increasing. We sought to assess clinical outcomes of ESD for EGC in elderly. Methods ESD was performed for patients with EGC, who fulfilled the criteria for ESD: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings 3 cm or less in diameter; and minute submucosal invasive cancer 3 cm or less in size. Two hundred and sixty elderly patients (≥75 years old) with 279 lesions, and 401 non-elderly patients with 434 lesions were enrolled to this study. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6–89 months (median: 30 months). Resectability (en-bloc or piecemeal resection), curability (curative or noncurative resection), completeness (complete or incomplete resection), complications, and survival rates were assessed. Rersults The one-piece resection rate was significantly lower in elderly patients (93.9%) than in non-elderly patients (97.9%). The complete resection rate was significantly lower in elderly patients (87.4%) than in non-elderly patients (96.6%). Pneumonia, but not bleeding or perforation, developed in association with ESD more frequently in the elderly patients by 2.2%. Local tumor recurrence was quite rare, and the overall and disease-free survival rates were acceptable irrespective of age. Conclusion En-bloc and complete resections were achieved less frequently in elderly patients, but the long-term outcomes in elderly EGC patients may be excellent, and ESD is a feasible treatment in the elderly.

Management of complications associated with endoscopic submucosal dissection/ endoscopic mucosal resection for esophageal cancer

Endoscopic resection of early esophageal cancer (EEC) is an established therapy in Japan and is increasingly becoming accepted and used regularly in other countries. Endoscopic submucosal dissection (ESD), an application of conventional endoscopic mucosal resection (EMR), has been developed to allow the resection of larger lesions in an en bloc manner; the earliest results so far have been promising even in EEC. ESD allows precise assessment of the histopathological curability of resected specimens, reducing local recurrence. However, ESD has relatively high complication rates; notification of perforation risk is essential especially in the esophagus. Bleeding during ESD can be managed by endoscopic closure with endoclips, and delayed bleeding is rare. Esophageal stricture following semicircular or complete circular esophageal ESD was relatively frequent even when treated by multiple pre‐emptive endoscopic balloon dilation. Endoscopic triamcinolone injection, temporal stenting and innovative transplantation of autologous tissue‐engineered epithelial cell sheets have shown promising results for the prevention of luminal stricture following semicircular esophageal ESD. In cases of circumferential ESD, however, giving oral prednisolone can offer a unique treatment option for the prevention of intractable post‐procedural stricture of the esophagus.

Endoscopic Submucosal Dissection for Colorectal Epithelial Neoplasms

PURPOSE: Endoscopic submucosal dissection permits removal of colorectal epithelial neoplasms en bloc, but long-term clinical outcomes remain unknown. METHODS: Endoscopic submucosal dissection was performed in 282 patients having 296 colorectal tumors that fulfilled the inclusion criteria, which included lesions greater than 20 mm in size for which en bloc resection would be difficult with endoscopic mucosal resection, lesions with fibrotic scar due to previous endoscopic treatment or biopsies, locally residual lesions after endoscopic resection, or invasive carcinoma with slight submucosal penetration. En bloc or piecemeal resection, complete (en bloc with tumor-free lateral/basal margins) or incomplete resection, and complications were assessed, and factors related to each were analyzed using logistic regression. Patients with early colon cancer received endoscopic follow-up and metastatic surveys for a median of 34 months. RESULTS: En bloc resection was achieved in 89.2% (264/296) and 234 lesions (79.1%) were deemed to have undergone complete resection. A right-side colonic location was the significant contributor to incomplete resection. Perforation was seen in 24 cases (8.1%) in association with tumor size and the presence of fibrosis. There was 1 case of locally recurrent tumor with incomplete resection, whereas neither recurrence nor residual disease was observed in the complete resection group. Neither cancer-related nor cancer-unrelated death was observed. CONCLUSIONS: Precise assessment of curability with successful en bloc resection may reduce tumor recurrence after endoscopic submucosal dissection. The prognosis of early colorectal cancer in patients treated by endoscopic submucosal dissection is likely to be excellent, although further longer follow-up studies are warranted.

Concentrations of α- and β-defensins in plasma of patients with inflammatory bowel disease

Abstract:Background:Impaired production/release of defensins, representative endogenous antimicrobial peptides, is associated with the pathogenesis of inflammatory bowel disease (IBD).Material and methods:Employing in house radioimmunoassay, we examined concentrations of the major forms α-defensins, human neutrophil peptides (HNP) 1–3 and human β-defensin (HBD)-2 in plasma of 55 IBD patients consisting of 29 patients with ulcerative colitis (UC) and 26 with Crohn’s disease (CD) and 57 controls.Results:The circulating HNP 1–3, but not HBD-2, levels in IBD patients were significantly higher than those in controls. Plasma HNP 1–3 concentrations in CD patients significantly correlated with Crohn’s disease activity index, peripheral white blood cell counts, serum CRP values and TNF-α levels.Conclusions:Elevation of circulating α-defensins levels is suggestive of their physiopathological roles in IBD. Plasma HNP 1–3 concentrations may be an indicator for CD activity and their association with CRP and TNF-α supports a possible association with the inflammatory process.