Association between Charlson comorbidity index and complications of endoscopic resection of gastric neoplasms in elderly patients.

BACKGROUND: Although endoscopic resection is safe and effective for gastric epithelial neoplasms, information is limited on its efficacy and safety in extremely elderly patients who have various comorbidities. Further, the relationship between comorbidities and complications of endoscopic resection is not well established. Therefore, we aimed to evaluate the efficacy and safety of endoscopic resection of gastric epithelial neoplasms in extremely elderly patients. METHODS: From October 2008 to December 2017, 4475 consecutive patients underwent endoscopic resection of gastric epithelial neoplasms. Among them, 242 were 75 years or older. We assessed Charlson comorbidity index (CCI) scores, procedural outcomes, and procedure- and sedation-related complications related to endoscopic resection. RESULTS: Mean patient age was 78.7 ± 3.2 years. Of the 242 patients, 124 (51.2%) had low-grade dysplasia and 112 (46.3%) had adenocarcinoma. The most common comorbidity was hypertension (55.4%), followed by diabetes (23.1%). The mean CCI score was 1.67 ± 1.43. Sixty patients (24.8%) had a CCI score ≥ 3. During the procedure, 10 (4.1%) patients had desaturation that recovered by flumazenil use with mask (n = 2) or Ambu bag (n = 3) ventilation. During subsequent admission, atelectasis or pneumonia occurred in 45 (18.6%) patients, post-procedural bleeding in 12 (5.0%), and perforation in 3 (1.2%). Respiratory complications were more common in patients with a CCI score ≥ 3 (20/60, 33.3%) than in those with a CCI score < 3 (25/182, 13.7%, P = 0.002). CONCLUSIONS: CCI score is related to respiratory complications of endoscopic resection in extremely elderly patients. Endoscopic resection must be performed cautiously, particularly in elderly patients with a high CCI score, to prevent respiratory complications.

Correction to: A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic extension of pyogenic liver abscess.

An amendment to this paper has been published and can be accessed via the original article.

Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease.

BACKGROUNDS: Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn's disease (CD). METHODS: A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. RESULTS: Median age of patients was 22.5 years (range, 15-49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months-54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). CONCLUSION: Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic extension of pyogenic liver abscess.

BACKGROUND: Transdiaphragmatic extension of pyogenic liver abscess is the rarest cause of pericarditis and pleural empyema. It is a rapidly progressive and highly lethal infection with mortality rates reaching 100% if left untreated. However, the transmission route, treatment methods and prognosis have not been well studied. CASE PRESENTATION: A 65-year-old male patient presented with a fever, dyspnea, and right upper quadrant abdominal pain. Computed tomography of the chest and abdomen showed huge liver abscess without full liquefaction in the left lobe, large amount of left pleural effusion, and mild pericardial effusion, and the patient was treated with parenteral antibiotics and pigtail insertion at the left pleura. However, four days later, cardiac tamponade was developed and surgical drainage of the abscess and pericardium was performed. Klebsiella pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the patient was discharged without any complications. CONCLUSIONS: Herein, we report a rare case of pleural empyema and pericarditis in that resulted from the extension of huge pyogenic liver abscess. Early surgical treatment may have prevented progression of the pericarditis to the more dismal purulent pericarditis. We also review pertinent English literature on pericarditis as a complication of PLA.

Self-expandable metal stents for the extraction of common bile duct stones in patients receiving dual antiplatelet agents: a pilot study.

BACKGROUND: Endoscopic sphincterotomy or endoscopic papillary balloon dilatation during endoscopic retrograde cholangiopancreatography (ERCP) are associated with a high risk of bleeding in patients receiving dual antiplatelet agents (APAs). However, the discontinuation of antiplatelet agents increases the risk of thromboembolic events in these patients. To date, the placement of self-expandable metal stents (SEMSs) in patients receiving dual APAs has not been well investigated. The aim of this study was to evaluate the feasibility and safety of SEMS placement for the removal of common bile duct (CBD) stones in patients in whom APAs were not discontinued. METHODS: Ten consecutive patients who were suspected of having CBD stones and who were receiving dual APAs were prospectively enrolled and underwent temporary SEMS placement, followed by stone extraction and SEMS removal. The patients continued taking dual APAs at the time of undergoing the procedure. RESULTS: SEMS placement was successful in all ten patients. Complete duct clearance with the SEMSs was achieved in a single session in all patients with CBD stones (9/9, 100%). One patient had cholangitis, but ERCP did not reveal biliary stones. There were no cases of bleeding during or after the procedure, even though all patients continued to take dual APAs. There were no new thromboembolic events. CONCLUSIONS: SEMSs can be used for the extraction of CBD stones in patients on dual APAs, and does not lead to hemorrhagic or thromboembolic events.

Restoration of common bile duct diameter within 2 weeks after endoscopic stone retraction is a preventive factor for stone recurrence.

BACKGROUND: Little information is available about the relationship between restoration of common bile duct (CBD) diameter after endoscopic stone retraction and recurrence of CBD stones in elderly patients. The present study was to determine whether restoration of CBD diameter is a preventive factor for CBD stone recurrence in elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). METHODS: From January 2006 to December 2010, 238 patients underwent the first and the second session of ERCP for the removal of CBD stones. Among them, 173 were over 65 years old. These patients were divided into recurrent group and non-recurrent group. Restoration of CBD diameter and patients' characteristics were compared. RESULTS: There was no statistical difference in patients' characteristics, associated diseases, or ERCP-related complications between the two groups. Reduction of CBD diameter was significantly larger in the non-recurrent group (2.7 ±â€¯1.7 mm) compared to that in the recurrent group (1.4 ±â€¯2.3 mm, P = 0.002). The proportion of patients with restoration of CBD diameter were significantly lower in the recurrent group (6/42, 14.3%) compared with that in the non-recurrent group (67/131, 51.1%) (P < 0.01). CONCLUSIONS: There is an inverse relationship between restoration of CBD diameter and CBD stone recurrence. Therefore, patients without restoration of CBD diameter within 2 weeks after endoscopic stone removal should be monitored more frequently.

Subjective taste to polyethylene glycol is associated with efficacy of right colon preparation.

AIM: A prospective observational trial with preparations using polyethylene glycol (PEG) to compare patient compliance and adverse events according to individual subjective taste. METHODS: A total of 299 outpatients (mean ± standard deviation [SD] 56.5 ± 13.8 years, 172 males) were recruited for our study. We assessed the efficacy of bowel preparation, subjective taste to their regimens, compliance and adverse events during the preparation. RESULTS: We achieved adequate preparation in 267 (89.3%). A total of 124 patients (41.5%) had 'unacceptable taste' to their regimens. The patients with acceptable taste had better compliance than the patients with unacceptable taste (p = .009). The patients with unacceptable taste had more frequent adverse events such as nausea, vomiting and abdominal bloating than the patients with acceptable taste (all p < .001, Table 2). Patients with unacceptable taste (16.1%) had more frequent inadequate preparation in overall colon than patients with acceptable taste (6.9%, p = .011). There was a significant difference in the efficacy of preparation of right colon between the two groups (p = .004). CONCLUSION: Subjective taste to PEG is associated with efficacy of right colon preparation. In addition, subjective taste to PEG is associated with compliance and adverse events.

Utility of baseline impedance level measurement in patients with gastroesophageal reflux symptoms.

OBJECTIVE: Twenty-four-hour multichannel intraluminal impedance (MII) and pH monitoring is used for detecting reflux episodes in patients with gastroesophageal reflux (GER) disease. However, the clinical significance of baseline impedance levels (BILs) has not been well studied. We aimed to evaluate whether BILs are related to various reflux events or acid-related parameters and to determine whether BILs during specific intervals could be substituted for 24-h BILs. MATERIAL AND METHODS: One-hundred forty-two patients GER symptoms underwent 24-h pH/impedance monitoring. We measured pH [(5 cm above the low esophageal sphincter (LES)] and BILs from three sites (3, 5, and 15 cm above the LES). RESULTS: Eighty-one subjects (57.0%) were diagnosed with gastroesophageal reflux disease, and 53 (37.3%) had acid reflux and 28 (19.7%) had nonacid reflux. The 24-h BILs at distal sites were lower in the "reflux" group than in the "no reflux" group (p < 0.001) and lower in the "acid reflux" group than in the "nonacid reflux" group (p < 0.001). However, there was no significant difference in 24-h BILs at the proximal site among the "no reflux", "acid reflux", and "nonacid reflux" groups. The interclass correlation coefficient value of 24-h BILs with daytime 6-h BILs was 0.916 (95% CI 0.882-0.940) and that with nighttime 6-h BILs was 0.909 (95% CI 0.871-0.935). CONCLUSION: BILs are related to GER, especially acid reflux. Location and duration of assessment for BILs needs to be standardized. Six-hour BILs could be substitutes for 24-h BILs. During analysis of MII-pH, more attention should be paid to BILs in the lower esophagus.

Endoscopic foreign body removal in the upper gastrointestinal tract: risk factors predicting conversion to surgery.

BACKGROUND/AIMS: Most foreign bodies of the upper gastrointestinal tract (UGIT) are successfully removed by endoscopic techniques without complications. However, some require conversion to surgery due to failure of endoscopic removal. The aim of this study was to analyze the risk factors predicting the need to convert to surgery after inability to endoscopically remove the foreign body. PATIENTS AND METHODS: The medical records of 885 patients treated between January 2006 and March 2014 for suspected foreign bodies in the UGIT were retrospectively reviewed. Patient characteristics, the type of foreign bodies, clinical outcomes, and risk factors predicting the conversion to surgery were analyzed. RESULTS: While endoscopic removal was successful in 94.7% (665/702) of the patients, the remaining 5.3% (37/702) needed conversion to surgery. There were no procedure-related deaths. According to the multivariate logistic regression analyses, older age (>70 years, p = 0.004), location (upper esophagus, p = 0.001), larger size (maximal diameter > 30 mm, p = 0.005), and longer impaction time (>40 h, p < 0.001) were significant risk factors predicting conversion to surgery due to inability to remove the foreign body endoscopically. CONCLUSIONS: Most of the foreign bodies in the UGIT were successfully removed by endoscopic techniques. However, surgical removal might need to be considered in patients with age >70 years, and those with foreign bodies in the upper esophagus, maximal diameter >30 mm, and impaction time >40 h, due to the possible high failure rate of endoscopic removal.

Intraductal US-directed management of bile duct stones without radiocontrast cholangiography.

BACKGROUND/AIMS: Intraductal US (IDUS) is an examination of the bile duct by using a thin-caliber ultrasonic probe, yielding real-time, high-quality cross-sectional images. We prospectively evaluated the feasibility and safety of IDUS-directed stone removal without radiocontrast cholangiography (RC) in naïve patients with common bile duct (CBD) stones. METHODS: A total of 38 naïve patients with suspected CBD stones (<20 mm) were enrolled in this study. If IDUS showed CBD stones, we performed endoscopic sphincterotomy and removed the identified CBD stones without RC. The primary outcome was success rate of CBD stone removal without RC. The secondary outcomes were conversion rate to conventional ERCP with RC, fluoroscopy time, clinical responses, and adverse events. RESULTS: IDUS was successfully performed in all enrolled patients (38/38, 100%). No echogenic material was observed in 3 patients (1 Mirizzi syndrome, 2 spontaneous passages of CBD stones). After endoscopic sphincterotomy, IDUS-directed stone removal was successfully performed without RC in 26 patients (74.3%) in the first session. In the 9 patients, after deployment of plastic stents, IDUS-directed stone removal was successfully completed without RC in a second session. There was no conversion to conventional ERCP with RC. Median fluoroscopy time was 10 seconds. There were no immediate and delayed adverse events related to the IDUS-directed stone removal. However, asymptomatic hyperamylasemia developed in 3 patients (7.9%), who recovered without adverse events. CONCLUSIONS: IDUS-directed stone removal without RC is feasible and safe for patients with CBD stones. We anticipate a potentially important role of IDUS in the field of various therapeutic interventions.

Pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for Helicobacter pylori eradication in a region with high rates of multiple drug resistance.

OBJECTIVES: Helicobacter pylori eradication rates with clarithromycin-based triple therapy are declining, and an alternative strategy is needed urgently. We sought to compare the efficacy of pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for H. pylori eradication in a region with high rates of multiple drug resistance. METHODS: Consecutive H. pylori-infected patients with gastric epithelial neoplasms were randomized to receive antimicrobial susceptibility-guided therapy or clarithromycin-based triple therapy for 7 days. In patients in whom the infection was not eradicated, antibiotics were given according to an initial antimicrobial susceptibility test as a second-line therapy in both groups. Eradication rates, antibiotics resistance rates, and drug compliance owing to adverse effects were compared between the groups. RESULTS: In total, 114 patients were enrolled, and 112 completed the protocols. Drug compliance and side effects were similar between the groups. The intention-to-treat eradication rates were 94.7% (95% confidence interval (CI)=88.8-100%, 54/57) in the antimicrobial susceptibility-guided group and 71.9% (95% CI=60.2-83.5%, 41/57) in the clarithromycin-based triple therapy group after the initial treatment (P=0.002), whereas the per-protocol (PP) eradication rates were 96.4% (95% CI=91.5-100%, 54/56) in the antimicrobial susceptibility-guided group and 73.2% (95% CI=61.5-84.8%, 41/56) in the clarithromycin-based triple therapy group (P=0.001). In H. pylori with clarithromycin resistance, the eradication failure rate with first-line treatment was lower in the susceptibility-guided therapy group (0%, 0/12) compared with the clarithromycin-based triple therapy group (80.0%, 95% CI=59.7-100%, 12/15) by PP analysis (P<0.001). CONCLUSIONS: Pretreatment antimicrobial susceptibility-guided therapy is more effective than clarithromycin-based triple therapy for H. pylori eradication in a region with high rates of multiple drug resistance.

Cap-assisted gastroscope versus cap-assisted colonoscope for examination of difficult sigmoid colons in a nonsedated Asian population: a randomized study.

BACKGROUND: Studies have estimated that cecal intubation failure occurs with conventional colonoscopy in about 10% of cases. Various methods have been adopted to improve the cecal intubation rate, including a transparent cap and special colonoscopes. OBJECTIVE: To assess the efficacy of using a cap-assisted gastroscope (E-cap) compared with a cap-assisted colonoscope (C-cap) for the complete examination of the colon in nonsedated patients with technically difficult sigmoid colons. DESIGN: Randomized, controlled study. SETTING: Tertiary-care referral center. PATIENTS: One hundred thirty-nine patients with technically difficult sigmoid colons were studied. INTERVENTION: Colonoscopy with either an E-cap (n = 69) or a C-cap (n = 70). MAIN OUTCOME MEASUREMENTS: Cecal intubation rate, cecal intubation time, patient-assessed pain score, and endoscopist-assessed pain score. RESULTS: The cecal intubation rate was significantly higher in the E-cap (65/69, 94.2%) than in the C-cap group (50/70, 71.4%; P < .0001). Patient-assessed pain (moderate to severe) was more frequently reported in the C-cap (14/70, 20.0%) than in the E-cap group (5/69, 7.2%; P = .029). Endoscopist-assessed pain (moderate to severe) was more frequently reported in the C-cap (13/70, 18.6%) than in the E-cap group (3/69, 7.2%; P = .009). For patients with a low body mass index (≤ 22 kg/m(2)), the cecal intubation rate was significantly higher in the E-cap (37/38, 97.4%) than in the C-cap group (15/29, 51.7%; P < .0001). LIMITATIONS: Single-center experience, lack of a gastroscope control group without a cap. CONCLUSION: The cap-assisted gastroscope is more tolerable and effective than cap-assisted colonoscope for the complete examination of the colon in patients with technically difficult sigmoid colons. ( CLINICAL TRIAL REGISTRATION NUMBER: KCT0000744.).

Cap-assisted ERCP in patients with difficult cannulation due to periampullary diverticulum.

Selective biliary cannulation is an essential prerequisite for therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The cap-fitted forward-viewing endoscope has been used for ERCP in patients with surgically altered anatomy. In this case series, 12 patients with periampullary diverticulum underwent ERCP using the cap-assisted forward-viewing endoscope due to failure of biliary cannulation using the standard technique. Successful ERCP was achieved in all patients with no serious complications.

Various applications of endoscopic scissors in difficult endoscopic interventions.

Endoscopic scissors offer a benefit over other devices by avoiding potential complications related to thermal and mechanical injury of surrounding structures. We describe our experience with endoscopic scissors in three difficult endoscopic interventions. A fishbone embedded in the esophageal wall penetrated very close to the pulsating aorta and the bronchus. The fishbone was cut in half by endoscopic scissors and removed without injury to adjacent organs. A gastric submucosal tumor with an insulated core that could not be resected by electrosurgical devices was cut using endoscopic scissors following endoloop placement. Extravascular coil migration after transcatheter arterial embolization resulted in a duodenal ulcer. The metallic coil on the duodenal ulcer was cut by endoscopic scissors without mechanical or thermal injury.

Needle-knife fistulotomy in patients with periampullary diverticula and difficult bile duct cannulation.

BACKGROUND AND AIM: Needle-knife fistulotomy has commonly been used for overcoming difficult bile duct cannulation. Periampullary diverticula (PAD) can be an impediment to endoscopic retrograde cholangiopancreatography (ERCP) procedures. There are little data on needle-knife fistulotomy in patients with PAD. We evaluated the efficacy and safety of needle-knife fistulotomy between patients with and without PAD. METHODS: Data from December 2005 to October 2010 were reviewed. Patients who underwent needle-knife fistulotomy were divided into the group with PAD and the group without PAD (control group). The technical success and complications were compared. RESULTS: A total of 3012 ERCP cases were analyzed. Needle-knife fistulotomy was performed in 154 out of 3012 cases (5.1%) with 138 of these patients (89.6%) experiencing successful bile duct cannulation. The overall cannulation success rate was not significantly different between PAD group (n=33) and control group (n =121) (93.9% vs 88.4%; P=0.523). There was no significant difference in pancreatitis, bleeding and perforation between the two groups. CONCLUSIONS: Needle-knife fistulotomy can be performed effectively and safely in patients with periampullary diverticula and difficult bile duct cannulation.

Therapeutic options for iatrogenic colon perforation: feasibility of endoscopic clip closure and predictors of the need for early surgery.

BACKGROUND: The therapeutic methods of iatrogenic colon perforation have not been performed despite the increasing rates of successful management by endoscopic clip closure. This study aimed to analyze the efficacy and complications of endoscopic clip closure and to identify the risk factors associated with the need for early surgery to avoid more invasive surgical interventions and adverse complications after endoscopic clip closure for iatrogenic colon perforation. METHODS: A retrospective multicenter review of the clinical course experienced by 32 patients with iatrogenic colon perforation who were treated using immediate endoscopic clip closure between January 2005 and December 2009 was performed. RESULTS: The technical success rate for endoscopic clip closure was 91% (29/32). After endoscopic clip closure, 22 patients (76%) required medical treatment for colon perforation, and seven patients (24%) had surgical treatment. Of the 22 patients who had only endoscopic clip closure, 17 (59%) had a favorable clinical course. Five patients had a long hospital stay with complication including abscess formation (three cases). Four patients underwent early surgery within 24 h, and laparoscopic simple closure was possible. But for three patients with surgery delayed more than 48 h, open laparotomy with colon resection including diversion were required. The risk factors associated with the need for early surgical treatment within 24 h after endoscopic clip closure were a large perforation [odds ratio (OR), 9.25; 95% confidence interval (CI), 1.85-46.20], leukocytosis (OR 6.58; 95% CI 1.86-23.29), fever (OR 5.05; 95% CI 1.05-24.28), severe abdominal pain (OR 4.30; 95% CI 1.17-15.83), and a large amount of peritoneal free air (OR 4.05; 95% CI 1.40-11.71). CONCLUSION: The endoscopic clip closure procedure can significantly reduce the frequency of surgery among patients with iatrogenic colon perforations. However, the decision for surgery must be made early after endoscopic clip closure to prevent adverse complications for patients with higher risk factors.

Usefulness of cap-assisted colonoscopy during colonoscopic EMR: a randomized, controlled trial.

BACKGROUND: Clinical demand for total colonoscopy is increasing. Several articles have reported on the usefulness of a cap for faster cecal intubation and reduced patient discomfort, but results for polyp and adenoma detection have been inconsistent. OBJECTIVE: To assess the efficacy of a cap attached to the tip of a colonoscope for detection and resection of polyps by experienced colonoscopists. DESIGN: Prospective, randomized, controlled trial. SETTING: A tertiary referral center. PATIENTS AND INTERVENTION: A total of 329 patients who underwent colonoscopic EMR were randomized to cap-assisted colonoscopy (CAC) (CAC group, n = 166) or regular colonoscopy (RC) (RC group, n = 163). MAIN OUTCOME MEASUREMENTS: Cecal intubation time, total procedure time, required time for colonoscopic EMR of each polyp, and missing polyp rate. RESULTS: The cecal intubation time in the CAC group and RC group was 5.3 ± 3.3 minutes and 5.8 ± 3.7 minutes, respectively (P = .170). The total procedure time in the CAC group and RC group was 23.0 ± 15.5 minutes and 29.2 ± 13.4 minutes, respectively (P = .626). The time required for colonoscopic EMR of each polyp in the CAC group and RC group was 3.5 ± 4.5 minutes and 4.2 ± 5.1 minutes, respectively (P = .010). The number of polyps during the initial colonoscopy in the CAC group and RC group was 2.2 ± 1.7 and 2.0 ± 1.8, respectively (P = .221). The number of detected polyps during colonoscopic EMR in the CAC group and RC group was 3.4 ± 2.7 and 2.7 ± 1.9 (P = .003). The number of missed polyps in the CAC group and RC group was 1.1 ± 1.5 and 0.8 ± 0.9 (P = .024). LIMITATION: Single-center experience. CONCLUSIONS: CAC may reduce the time required for colonoscopic EMR of each polyp and may also improve the polyp detection rate.

Expression of KITENIN in human colorectal cancer and its relation to tumor behavior and progression.

KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of current study was to evaluate whether KITENIN affects tumor cell invasion and prognosis in human colorectal cancers. We investigated the biologic role of KITENIN on tumor cell invasion by using small interfering RNA in Caco2, DLD1, and SW480. We evaluated the expression of KITENIN and activator protein-1 (AP-1) target genes in human colorectal cancer tissues. The tumor cell invasion was decreased by knockdown of KITENIN in three tested cell lines. The mRNA expression of cyclin D1 and COX-2 was decreased in KITENIN knockdown Caco2 and the mRNA expression of MMP-3 and COX-2 was decreased in KITENIN knockdown DLD1 and SW480. The extracellular-signal protein kinase 1/2 (ERK1/2) phosphorylation was decreased in KITENIN knockdown in three tested cell lines. Expression of KITENIN and AP-1 target genes was significantly increased in human colorectal cancer tissues. The ERK1/2, c-Jun N-terminal kinase (JNK) and p38 phosphorylations were increased in human colorectal cancer tissues. Expression of KITENIN was significantly associated with lymphovascular invasion, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN is associated with human colorectal cancer progression including invasion and metastasis.

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.