Woong Cheul Lee

The accuracy of probe-based confocal endomicroscopy versus conventional endoscopic biopsies for the diagnosis of superficial gastric neoplasia (with videos).

BACKGROUND Probe-based confocal laser endomicroscopy (pCLE) allows real-time in vivo histologic evaluation of GI mucosal lesions. Although pCLE has been used for various GI disorders, the significance of pCLE for gastric lesions is largely unknown. OBJECTIVE We compared the accuracy of conventional endoscopic forceps biopsy and pCLE for the diagnosis of superficial gastric neoplasia before endoscopic resection. DESIGN Prospective comparative study. SETTING Single tertiary referral center. PATIENTS This study involved 54 superficial gastric neoplasias in 46 patients. MAIN OUTCOME MEASUREMENT Accuracy of in vivo and offline pCLE diagnosis and interobserver agreement. METHODS pCLE was performed before endoscopic resection of superficial gastric neoplasias previously diagnosed by endoscopic biopsy. The overall accuracy of endoscopic, in vivo pCLE, and offline pCLE diagnosis was compared with postendoscopic resection histopathology. RESULTS Endoscopic resection was performed on 54 lesions. On final histopathology, there were 3 non-neoplastic lesions, 19 gastric dysplasias, 22 differentiated adenocarcinomas, and 10 undifferentiated adenocarcinomas. The overall agreement with the final histopathology was substantial for conventional biopsies (κ = 0.617) and excellent for in vivo pCLE (κ = 0.824) (P < .001). The overall accuracy for the diagnosis of adenocarcinoma was 91.7% for pCLE and 85.2% for conventional biopsies (P = .065). The combined accuracy of conventional endoscopic biopsies and pCLE was 98.1%. The interobserver agreement for offline pCLE diagnosis was excellent (κ = 0.931). LIMITATIONS Single-center study, small sample size. CONCLUSION Our study showed that pCLE can provide an accurate diagnosis for superficial gastric neoplasia. pCLE has the potential to compensate for the inherent limitations of a conventional endoscopic biopsy.

Double guidewire technique vs transpancreatic precut sphincterotomy in difficult biliary cannulation

AIM To compare the outcomes between double-guidewire technique (DGT) and transpancreatic precut sphincterotomy (TPS) in patients with difficult biliary cannulation. METHODS This was a prospective, randomized study conducted in single tertiary referral hospital in Korea. Between January 2005 and September 2010. A total of 71 patients, who bile duct cannulation was not possible and selective pancreatic duct cannulation was achieved, were randomized into DGT (n = 34) and TPS (n = 37) groups. DGT or TPS was done for selective biliary cannulation. We measured the technical success rates of biliary cannulation, median cannulation time, and procedure related complications. RESULTS The distribution of patients after randomization was balanced, and both groups were comparable in baseline characteristics, except the higher percentage of endoscopic nasobiliary drainage in the DGT group (55.9% vs 13.5%, P < 0.001). Successful cannulation rate and mean cannulation times in DGT and TPS groups were 91.2% vs 91.9% and 14.1 ± 13.2 min vs 15.4 ± 17.9 min, P = 0.732, respectively. There was no significant difference between the two groups. The overall incidence of post- endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis was 38.2% vs 10.8%, P < 0.011 in the DGT group and the TPS group; post-procedure pancreatitis was significantly higher in the DGT group. But the overall incidence of post-ERCP hyperamylasemia was no significant difference between the two groups; DGT group vs TPS group: 14.7% vs 16.2%, P < 1.0. CONCLUSION When free bile duct cannulation was difficult and selective pancreatic duct cannulation was achieved, DGT and TPS facilitated biliary cannulation and showed similar success rates. However, post-procedure pancreatitis was significantly higher in the DGT group.

Clinically Useful Diagnostic Tool of Contrast Enhanced Ultrasonography for Focal Liver Masses: Comparison to Computed Tomography and Magnetic Resonance Imaging

Background/Aims To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses. Methods CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI. Results The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765. Conclusions If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.

Double-Balloon Enteroscopy in Elderly Patients: Is It Safe and Useful?

Background/Aims Providers may be hesitant to perform double-balloon enteroscopy (DBE) in the elderly because the increased number of co-morbidities in this population poses a greater risk of complications resulting from sedation. There are limited data on the use of DBE in the elderly. Here, we assessed the safety and efficacy of DBE in the elderly compared to those in younger patients. Methods We retrospectively analyzed the medical records of 158 patients who underwent 218 DBEs. Patients were divided into an elderly group (age ≥65 years; mean 71.4±5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5±13.5; n=124; 177 DBEs). Results In both groups, the most common indication for DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%; P=0.002) were the most common finding in both groups, followed by tumors (30.8% vs. 14.1%; P=0.036). The elderly were more likely to receive interventional therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically significant. The therapeutic success rate of DBE was 100% in the elderly group compared to 87.5% in the younger group (P=0.536). The overall DBE complication rate was 1.8% overall, and this rate did not differ significantly between the groups (2.6% vs. 1.7%; P=0.548). Conclusions DBE is safe and effective in the elderly, and has a high diagnostic yield and high therapeutic success rate.

TRAIL enhances apoptosis of human hepatocellular carcinoma cells sensitized by hepatitis C virus infection: therapeutic implications.

Hepatitis C virus (HCV) infection causes chronic liver diseases leading to hepatocellular carcinoma (HCC) and liver failure. We have previously shown that HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for cancer therapy, their potential against HCC with chronic HCV infection has not been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of caspase-8 leading to elevation of apoptotic signaling in infected cells and also present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8, caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV-induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8 signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase (PARP), a substrate for caspase-3 during apoptosis, indicating the functional role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating the effect of TRAIL for the induction of selective apoptosis of HCC cells infected with HCV. Given the importance of apoptosis in HCC development, our data suggest that HCV-induced DR4 and DR5 may be considered as an attractive target for TRAIL therapy against HCC with chronic HCV infection.

Staging accuracy of endoscopic ultrasound performed by nonexpert endosonographers in patients with resectable esophageal squamous cell carcinoma: is it possible?

The accuracy of endoscopic ultrasound (EUS) is operator-dependent. According to learning curve study, the accuracy of EUS T-staging for esophageal cancer has been reported to be greater in an investigator who had performed at least 100 EUS examinations. We determined comparative study regarding T-staging accuracy of EUS for esophageal squamous cell carcinoma between expert and nonexpert endoscopic ultrasonographers. We retrospectively identified 73 consecutive patients with esophageal squamous cell carcinoma who underwent EUS and endoscopic mucosal resection, endoscopic submucosal dissection, or surgery. EUS was performed by expert (Group 1) and nonexpert (Group 2) endoscopic ultrasonographers in multitertiary hospitals. Groups 1 and 2 were 37 and 36 patients during 2005-2011, respectively. Forty-two patients (57.5%) of the overall patients underwent surgical exploration. Correct endoscopic ultrasonographic T-staging of Group 1 was observed in 34 (91.9%) patients, while that of Group 2 was observed in 26 (72.2%) patients. And there was significant difference in correct endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.035). The incorrect endoscopic ultrasonographic T-staging of Group 1 were three cases that were overstaging (8.1%), but in Group 2 there were seven overstaging (19.4%) and three understaging (8.3%). There was no significant difference in overstaging or understaging of incorrect endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.528). This study first provides evidence that endoscopic ultrasonographic T-staging of nonexpert endoscopic ultrasonographers was inferior to be correct, compared with that of expert endoscopic ultrasonographers. EUS staging for esophageal cancer should be performed by expert endoscopic ultrasonographers to provide appropriate management strategy.

Endoscopic Treatment of Various Gastrointestinal Tract Defects with an Over-the-Scope Clip: Case Series from a Tertiary Referral Hospital

Recently, increasingly invasive therapeutic endoscopic procedures and more complex gastrointestinal surgeries such as endoscopic mucosal resection, endoscopic submucosal dissection, and novel laparoscopic approaches have resulted in endoscopists being confronted more frequently with perforations, fistulas, and anastomotic leakages, for which nonsurgical closure is desired. In this article, we present our experiences with the use of over-the-scope clip (OTSC) for natural orifice transluminal endoscopic surgery (NOTES) closure, prevention of perforation, anastomotic leakages, and fistula closures. The OTSC is a valuable device for closing intestinal perforations and fistulas, for NOTES closure, and for the prevention of perforation after the excision of a tumor from the proper muscle layer. Furthermore, it seems to be quite safe to perform, even by endoscopists with little experience of the technique.

Clinical Features of Drug-induced Liver Injury According to Etiology.

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.

Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett’s esophagus

AIM To determine whether magnified observation of short-segment Barretts esophagus (BE) is useful for the detection of specialized intestinal metaplasia (SIM). METHODS Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to × 80. The magnified images were analyzed with respect to their pit-patterns, which were simultaneously classified into five epithelial types [I (small round), II (straight), III (long oval), IV (tubular), V (villous)] by Endos classification. Then, a 0.5% solution of methylene blue (MB) was sprayed over columnar mucosa. The patterns of the magnified image and MB staining were analyzed. Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy. RESULTS Three of five patients with a type V (villous) epithelial pattern had SIM, whereas 21 patients with a non-type V epithelial patterns did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pit-patterns in detecting SIM were 100%, 91.3%, 92.3%, 60% and 100%, respectively (P = 0.004). Three of the 12 patients with positive MB staining had SIM, whereas 14 patients with negative MB staining did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MB staining in detecting SIM were 100%, 60.9%, 65.4%, 25% and 100%, respectively (P = 0.085). The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemars test (P = 0.0391). CONCLUSION The magnified observation of a short-segment BE according to the mucosal pattern and its classification can be predictive of SIM.

Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C

Background/Aims This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. Methods This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. Results SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). Conclusions Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.