Seok Reyol Choi

Long-term outcomes of endoscopic submucosal dissection in gastric neoplastic lesions at a single institution in South Korea

Abstract Objective. Although endoscopic treatment for early gastric cancer (EGC) is an accepted therapy in South Korea and Japan, long-term outcomes remain unknown. We evaluated the clinical outcome of endoscopic submucosal dissection (ESD) for gastric dysplasia and EGC. Material and methods. A total of 402 patients with gastric dysplasia and EGC were treated with ESD at a single hospital from January 2004 to December 2007. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 9–49 months (median 30 months). Resectability (en bloc or piecemeal resection), curability (complete or incomplete), local recurrence, and disease-free survival rates were estimated. Results. There were 107 patients with low-grade dysplasia (LGD), 97 with high-grade dysplasia (HGD) and 198 with EGC. In EGC patients, en bloc resection was achieved in 89.7% (177/198), the complete resection rate was 87.9% (174/198), and the local recurrence rate was 5.1% (10/198). Tumor size >20 mm was significantly associated with local recurrence (odds ratio 6.45; 95% CI 1.20–20.11; p=0.001). There were significant correlations between the incidences of a piecemeal or incomplete resection and that of local recurrence (odds ratio 5.23; 95% CI 1.02–18.34; p=0.001; and odds ratio 6.99; 95% CI 1.22–21.65; p=0.002, respectively). The 3-year cancer-free survival rate was 94.9%. Conclusions. Curative treatment with successful en bloc resection can reduce the local recurrence of gastric neoplastic lesions after ESD. Clinical outcome may be excellent, although longer follow-up studies are warranted.

Optical biopsies by confocal endomicroscopy prevent additive endoscopic biopsies before endoscopic submucosal dissection in gastric epithelial neoplasias: a prospective, comparative study.

BACKGROUND Confocal laser endomicroscopy (CLE) allows real-time in vivo histologic evaluation of GI lesions. To our knowledge, there is no reported prospective study comparing endoscopic and optical biopsy using CLE before endoscopic submucosal dissection (ESD) with post-ESD histopathology. OBJECTIVE We compared endoscopic and optical biopsy before ESD and thereby assessed the ability of CLE to effectively diagnose and differentiate gastric epithelial neoplasia. DESIGN Single tertiary-care center, prospective comparative study. SETTING Soonchunhyang University Hospital, between September 2009 and April 2010. PATIENTS This study involved 31 patients with 35 gastric epithelial neoplasias, previously diagnosed by endoscopic biopsy, who were scheduled for ESD. INTERVENTION Target lesions were imaged in vivo by using CLE. MAIN OUTCOME MEASUREMENTS The overall accuracy of endoscopic and CLE diagnosis was compared with post-ESD histopathology. RESULTS In histopathology after ESD, 11 of 35 lesions (31.5%) were adenomas and 24 (68.5%) were adenocarcinomas. The overall accuracy of CLE diagnosis of gastric adenomas and adenocarcinomas was significantly higher at 94.2% (95% confidence interval [CI], 81.3-98.4), versus 85.7% (95% CI, 70.6-93.7) for endoscopic biopsy (P = .031). The overall accuracy of CLE diagnosis of differentiated and undifferentiated adenocarcinomas also was higher (95.4%; 95% CI, 78.2-99.1) than that of endoscopic biopsy (84.2%; 95% CI, 62.4-94.4) but did not differ significantly (P = .146). LIMITATIONS Single tertiary-care center experience and small patient number. CONCLUSION This study demonstrates the high accuracy of diagnosis of gastric epithelial neoplasia by using CLE. The use of CLE could possibly thus reduce the number of unnecessary biopsies and mistaken diagnoses before ESD.

A study of metachronous cancer after endoscopic resection of early gastric cancer

Abstract Objective. Endoscopic resection is commonly used for early gastric cancer (EGC) in Korea and Japan. There are only a few reports of metachronous cancer after endoscopic resection. The aim of this study was to identify clinical factors associated with metachronous gastric cancer after endoscopic resection. Methods. A total of 176 patients with EGC who had underwent endoscopic submucosal dissection (ESD) were periodically followed-up with endoscopic examinations from January 2004 to December 2007. The incidence and variable factors of metachronous gastric cancer were investigated in a retrospective study. Results. The median interval between the diagnosis of primary cancer and the diagnosis of the first metachronous cancer was 30 months (range 18–42 months). Metachronous gastric cancer had developed in nine patients (5.1%) during follow-up period and seven patients (4.0%) had synchronous gastric cancer lesions within 1 year of the initial endoscopic treatment. Annual incidence rate of metachronous cancer was approximately 3.3%. Antrum atrophy and old age were significantly associated with the incidence of metachronous cancer. The status of Helicobacter pylori, size, location and gross finding of lesion had no significant relationship with metachronous occurrence. Conclusions. We should examine more carefully older patients who have atrophic gastritis because secondary cancer including metachronous cancer might occur in remnant stomach after initial successful endoscopic resection. And prospective study will be needed for the optimal endoscopic surveillance interval.

Risk factors for immediate and delayed bleeding associated with endoscopic submucosal dissection of gastric neoplastic lesions

Abstract Objective. Endoscopic submucosal dissection (ESD) of gastric neoplasia has been reported to have a higher bleeding rate than conventional endoscopic mucosal resection (EMR). The aim of this study was to identify the risk factors for bleeding associated with ESD. Material and methods. The records of consecutive patients who underwent ESD for gastric adenoma/early gastric cancer were reviewed. Potential risk factors included patient age, lesion size, gross findings, location, and histology of the tumor. The primary end-point was the incidence of immediate or delayed bleeding related to ESD. Results. A total of 144 patients were studied; bleeding occurred in 32 cases (22.2%) with immediate bleeding in 29 cases. Delayed bleeding (3 cases) occurred at day 2 (2 patients) and at day 7 in 1 patient. In all cases of immediate bleeding, immediate hemostatic therapy was successful. The histology of tumor was the only factor that was statistically significantly associated with bleeding (adjusted hazard ratio 6.770, 95% confidence interval 1.830–25.048, p=0.004). Conclusions. The only factor that correlated with an increased risk of bleeding with ESD was the presence of gastric malignancy. We found no factor that would, prospectively, be amenable to prevention of bleeding.

Involvement of Na+-leak Channel in Substance P-induced Depolarization of Pacemaking Activity in Interstitial Cells of Cajal

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal muscles that generate the rhythmic oscillations in membrane potential known as slow waves. ICCs also mediate or transduce inputs from the enteric nervous system. Substance P (SubP) is a member of the family of mammalian tachykinin peptides that are predominantly released by enteric neurons. This study assessed the relationship of Na+-leak channel (NALCN) in the SubP-induced depolarization in pacemaking activity in the gastrointestinal tract. The patch-clamp technique for whole-cell recording was used in cultured cluster and single ICCs. Electrophysiological and pharmacological properties of SubP in ICC pacemaking activity were similar to those of NALCN. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of NALCN messenger RNA and protein in mouse small intestine. NALCN is involved in the SubP-induced depolarization of intestinal pacemaking activity. The protein is a potential target for pharmacological treatment of motor disorders of the gut.

Development and validation of a Functional Dyspepsia‐Related Quality of Life (FD‐QOL) scale in South Korea

Background:  Quality of life (QOL) in patients with functional dyspepsia in South Korea has never been studied, mostly due to the lack of a psychometrically validated disease‐specific instrument for measuring the QOL. The aim of the present study was to develop and validate a QOL scale for patients with functional dyspepsia.

Early detection of recurrence after endoscopic treatment for early gastric cancer

Objective. Although there have been many reports regarding clinical outcomes of endoscopic treatment for early gastric cancer (EGC), little is known about detection of recurrence after endoscopic submucosal dissection (ESD). This study aims to clarify the clinical value of serological marker or imaging tools, including conventional CT and PET-CT scans, in detecting recurrent gastric cancer after ESD in Korea. Material and methods. From July 2004 to March 2008, 212 patients who had received ESD for EGC were enrolled in the study. For preoperative staging, conventional CT and PET-CT scans were performed in 141 patients, and for detection of recurrence of cancer, conventional CT, PET-CT scans and tumour marker; CEA, CA19-9, AFP were checked in 165 patients. Results. The local recurrence rate was 4.7% (10/212) during the study period. At 9 months after endoscopic treatment, 3 cases recurred. Four showed recurrence at 12 months, 2 at 18 months and 1 at 24 months. The positive rate was 7.1% (10/141) in conventional CT and 0% (0/24) in PET-CT scans for preoperative staging. Conventional CT and PET-CT scans could not detect local recurrence of cancer during the follow-up period. Tumour markers did not show any significant correlation with recurrence of cancer. Conclusions. The study suggests that conventional CT, PET-CT scans and tumour marker have no role in the primary surveillance of early gastric cancer and/or in detecting recurrence after endoscopic treatment. For early diagnosis of recurrence after endoscopic treatment, a biopsy specimen from the endoscopic examination has to be obtained at regular intervals.

Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

Inhibition of pacemaker activity in interstitial cells of Cajal by LPS via NF-κB and MAP kinase

AIM To investigate lipopolysaccharide (LPS) related signal transduction in interstitial cells of Cajal (ICCs) from mouse small intestine. METHODS For this study, primary culture of ICCs was prepared from the small intestine of the mouse. LPS was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp technique. Immunocytochemistry was used to examine the expression of the proteins in ICCs. RESULTS LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809, a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-L-arginine Methyl Ester, an inhibitor of nitric oxide (NO) synthase. Toll-like receptor 4, inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ICCs. Catalase (antioxidant agent) had no action on LPS-induced action in ICCs. LPS actions were blocked by nuclear factor κB (NF-κB) inhibitor, actinomycin D (a gene transcription inhibitor), PD 98059 (a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases (MAPK) inhibitor]. SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not NO. CONCLUSION LPS inhibit the pacemaker currents in ICCs via prostaglandin E2- and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-κB are implicated in these actions.

Gastric glomus tumor: analysis of endosonographic characteristics and computed tomographic findings.

Among submucosal tumors (SMT), gastric glomus tumors are rare vascular tumors, and only a few cases where glomus tumors have been differentiated from other mesenchymal tumors by endoscopic ultrasonography (EUS) or computed tomography (CT) have been reported. In this case series, we aimed to analyze the EUS and CT characteristics of gastric glomus tumors. Seven patients with gastric glomus tumors were retrospectively enrolled in this study. EUS showed that all the tumors were located in the fourth EUS layer (muscularis propria) and had distinct borders. The tumors had a heterogeneous appearance with either hypo‐ or hyperechogenicity, and all the tumors except one had the characteristic peripheral halo around them. On CT scans,all the tumors appeared as well‐defined SMT with a clear margin and showed the same characteristics in the different phases of CT. During dynamic contrast‐enhanced CT, the tumors showed strong enhancement in the arterial phase and prolonged enhancement in the delayed phase. This case series shows the characteristic EUS findings and the distinguishing features of CT scans for gastric glomus tumors; these findings will help in differentiating gastric glomus tumors from other SMT.